Flaraxin

Website :: www.flaraxin.com E-mail : stccc.phoenix.ua@gmail.
com
FLARAXIN
Scientific & Treatment Center for Cancer Curing PHOENIX
FLARAXIN IS EFFECTIVE IN 90% OF ONCOLOGIC DISEASES

FLARAXIN is a non-toxic anti-tumoral phytopreparation, interferonogene, stimulating tumoral necrosis factor,destroys tumoral tissue. Immunomodulator and antioxidant. Prevents metastatic spreading and relapse.
Methods worked out in Scientific & Treatment Center for Cancer Curing PHOENIX (License of the Ukrainian Ministry of Health Seria 299302) that allow to realize the effective treatment of the patients, not to be treated by traditional methods.
Website : www.flaraxin.com E-mail : stccc.phoenix.ua@gmail.com
CONTENT
INFORMATION ABOUT STCCC PHOENIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 CONTACT INFORMATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4 THE HISTORY OF THE FLARAXIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 III-rd AND IV-th STAGE OF MALIGNANT NEOPLASM TREATMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6 FLARAXIN APPLICATION EFFICIENCY IN DIFFERENT CASES WITH CANCER . . . . . . . . . . . . . . . . . . . . . . . . . . . .9 FLARAXIN INSTRUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 TREATMENT SCHEME . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 FLARAXIN Questions and answers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 EXTRACT 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 REPORT on the results of clinical trials of new anticancer drug FLARAXIN / 1 phase of research / . . . . . . . . . . . .15 EXTRACT 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 REPORT on the result of clinical trial of new anticancer drug FLARAXIN / 2 phase of reseach /. . . . . . . . . . . . . . .22 REPORT on the results of clinical trials of new anticancer drug FLARAXIN /2 extended phase of research/;. . . . . .24 EXTRACT 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 REPORT ON THE TRIAL OF INTERFERONOGENIC ACTIVITY OF ANTITUMORAL PREPARATION FLARAXIN . . . . . . .36 EXTRACT FROM THE REPORT ON THE TRIAL OF IMMUNOMODULATING CHARACTERISTICS OF THE FLARAXIN . . 38 PATHOPHYSIOLOGICAL MECHANIZMS OF ANTIPROLIFERATIVE FLARAXIN EFFECT REALIZATION . . . . . . . . . . . .39 EXECUTION OF THE TEST ON SELECTIVE CONNECTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..41 ESTIMATION OF ANTIOXIDANT ACTIVITY OF FLARAXIN ON STARTING STAGES OF FREE-RADICAL OXIDATION. ..42 CLINICO-MORPHOLOGICAL CHARACTERISTICS OF TUMORS AFTER FLARAXIN ACTION. . . . . . . . . . . . . . . . . . . 44 LIST OF PATIENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..51
INFORMATION ABOUT STCCC PHOENIX
STCCC Phoenix founded in 1996 to coordinate research work on a comprehensive study of a new anticancer drugs of plant origin -FLARAXIN (historical background), which was developed in the Kiev Research Institute of Pharmacology and Toxicology by the surgical oncologists Kulik Ivan Anisimovich. STCCC Phoenix developed and clinically tested a number of biologically active preparations of plant origin. For the first time, has been used a unique technology of plant concentrates, allowing several times to increase the biological activity of number natural substances. As a result of comprehensive research has developed a number of medical treatments for cancer patients by the FLARAXIN together with a number of biologically active preparations. The practice of their application showed the effectiveness of their impact on a number of infectious, virus, somatic and cancer diseases. For early detection of cancer, as well as possible recurrence introduced the latest techniques of early detection. The method of professor Shahbazov predicts the impact of a drug to identify pathology. Now medications of STCCC "Phoenix" are used, as in oncology clinics, and medical centers of Ukraine and Russia.
PRIORITIES OF THE CENTER Optimization of the existing methods of treatment for cancer patients combining the use of surgery, chemotherapy and radiotherapy and FLARAXIN in various combinations. Application of our medications for the profilactics and prevention of recidivation, after medical investigation and ascertainment of diathesis to tumors. The prevention and elimination of possible recurrence of the disease. Consultation of the patients about non-toxic treatment of tumors. Provide scientific and technical assistance to a wide range of health professionals on the practical application of biologically active drugs in the treatment of infectious parasitic disease, somatic and cancerpathology. The research, development and clinical testing of new drugs of vegetable origin derived from the vacuumcondensing and drying technology.
CONTACT INFORMATION
Please indicate to whom the E -mail is addressed stccc.phoenix.ua@gmail.com or leave a message by phone and we will contact you back as soon as possible. Englisch ,Deutsch,Nederlands & speaking For Europe Tel: +44 20 8133 8062 For Asia Tel: +85 281 25 25 72 phoenix.flaraxin
Helena Oleynik Doctor Russian speaking only Consultation is free of charge. Write your questions by: stccc.phoenix.ua@gmail.com by the phone Russian speaking only : +38 (067) 571 7764 Working time: Mo.-Fr. 9:00-17:00, Sa. 9:00-13:00.
----------------------------Michail Kolychev - Director Russian speaking only el: +38 (067) 576 0988 Fax: +38 (057) 705 6271 -------------------------------Andrey Bogdan - Manager English and Russian speaking Tel: +38 (067) 571 77 64 --------------------------------
Our address : Svobody sq. 7, office 378, 61022-Kharkiv, Ukraine
THE HISTORY OF THE FLARAXIN
The preparation Flaraxin was first studied in the period from 1985 to 1990.
According to the data of the preparation clinical trial it was established that Flaraxin is a remedy of vegetable origin, active components of which are vegetable polyphenoles. During the trial it was found out that Flaraxin has the ability to stimulate the secretion of endogenic interferon and the neoplasm necrosis factor, promotes immunologic background normalization and smoothes out the correlation of immunocomponent cells CD4/CD8 (helpers-suppressors) and increases the number of natural killers (NKcells). During the immune-biochemical trial the ability of Flaraxin to connect with oncophetal proteins, causing their micro-denaturation damages was established. Cancerostatic effect was explicated by Flaraxin influence on metabolism of neoplasm cells, causing their death. Clinical trial of the preparation Flaraxin was carried out on the basis of oncology department of Kiev medical institute in the period from September 1990 to January 1991 and in Kiev Oncology SRI under oncologic process in the stage of neglect desolation in patients with melanoblastoma in the period from December 1992 to October 1993.
III-rd AND IV-th STAGE OF MALIGNANT NEOPLASM TREATMENT

Is it possible to bring the disease into absolute remission? Methods worked out in Scientific and Treatment Center for Cancer Curing PHOENIX (License of the Ukrainian Ministry of Health Seria 299302) that allow to realize effective treatment of the patients, not to be treated by traditional methods. FLARAXIN (F.) is a non-toxic anti-tumoral phytopreparation, interferonogene, stimulating tumoral necrosis factor, destroys tumoral tissue. Immunomodulator and antioxidant. Prevents metastatic spreading and relapse.
Therapeutic peculiarities with Flaraxin. are: Excellent endurability of the preparation; Absence of collateral phenomena under high anti-tumoral activity; High possibility to bring the tumor into full remission; Prevention of disease relapse and metastasis spreading prophylactics; Absence of toxic manifestations, which is explained by F. high constituency. Flaraxin. can be used by the patients: having chemo- or radiotherapy (F. is combined with Polychemotherapy (PCT) and X-ray therapy) ; with inoperable form of the disease; not subjected to radial therapy; with expressed allergic reaction on administration of chemotherapeutic preparations; weakened; Pharmacologic activity of Flaraxin: Able to connect and blocking the oncological proteins, causing their death; Increases the number of natural killers (NK-cells) T-lymphocites; Stimulates endogenic interferon and tumor necrosis factor production; Normalize immunological background (removes immune violations); Normalizes correlations of immune cells CD4/CD8 (helpers-suppressors); Flaraxin. is effective under: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Cerebrum (Brain) cancer (glioma, ependymoma, oligodendroglioma, nervinoma etc.); Skin cancer (melanoma, melanoblastoma, etc.); Lung cancer; Breast cancer; Stomach cancer; Bladder cancer; Colorectal cancer; Colon cancer; Female sexual sphere cancer (uterus, cervix, ovarium); Prostate cancer (adenoma); Mediastinal cancer; Under non-malignant neoplasm of various locality.
Clinical application of Flaraxin. is advisable in the following cases: 1) F. is advisable to use in patients with pretumoral proliferative processes as well as in patients with minimal tumoral process, after radical surgical treatment when it is necessary to lead reconstruction of anti-tumoral resistance of organism and its homeostatic mechanisms; Treatment with F. can be either basic or background, precede polychemotherapy and radiotherapy, besides it can be used in intervals between treatment cycles as well as the preparation for attained results stability, in the process of classical anti-tumoral therapy. It is stipulated for its minimal toxic effect and influence choice on tumor tissue. In patients with spread tumoral process it is advisable to use F. in complex polychemotherapy, radiotherapy, using its specific anti-tumoral activity and protective properties. Under inability to conduct chemo- and radial therapy F. is used independently.
2)
3) 4)
According to its chemical properties F. is compatible with many anti-tumoral remedies excluding metal-containing, as it has abilities to complex-formation. If included into treatment scheme Flaraxin. reducing: Cardiotoxicity, specified by lypooxigenesis activation, typical to antibiotics of antracyclic group; Neurotoxicity - like preparations of vinca-class (Vincristin, Vinblastin); Pyramidal disorders and syndrome of orthostatic hypotension like Fluorouracil; Myelotoxic effect and immunodepression - like alkylating preparations, etc. Flaraxin. should be included into the following treatment schemes of oncologic patients: Known methods of oncological patients treatment (chemotherapeutic, radial, and surgical) is accompanied by powerful immune suppression, which considerably suppresses immune system function, closing vicious circle of tumoral process. [4,8]. Chemotherapy envisages the use of remedies, having a number of reactionally capable groupings, denaturating proteins of not only tumoral, but also normal cells, by which their high toxicity for the organism can be explained. F. conducts with not only tumoral cells, causing their death, in this case it does not influence hematogenesis, organs of breathing, excretory and digestive systems, CNS, skin, etc. Being powerful immunomodulator it does not suppress immune system, but it raises its level of functional activity. Prescribing F. before chemotherapy it is necessary to take into consideration some of its peculiarities. Under the influence of F. tumoral cells become more vulnerable relative to the factors of natural anti-tumoral immunity and anti-tumoral cytostatics. That is why for more effective treatment with F. it is necessary to have initial immune-biochemical indices of the patient, especially under preparation for chemotherapy. It is necessary to prescribe F. under low level of natural killers cytastatic activity (lower 40% - by all means, from 50 to 55% - preferably); in presence of initial non-protein S-groups, in blood serum (spontaneous disproteinemy with autoimmune aggression); as well as under violation of oxidation-reductive (SH-SS) potential of serum proteins. These violations are often combined with each other. If 8 prescribed injections of F. normalized the violations mentioned above, the chemotherapy can be started. If optimal immune-biochemical indices after 8 injections are not achieved on the background of positive dynamics, it is reasonable to prescribe 8 more injections. If it is impossible to lead at least one from presented immune-biochemical tests, it is possible to guide on clinical picture of the disease course. Under noted subjective improvement after first 8 injections of F. 8 more injections can be repeated. If some subjective or objective indications are absent, the following injections are not desirable. It is impossible to continue injections when individual intolerance towards the preparation appears. In such cases it is preferable to insert preparations lowering auto-allergic incite of the organism (cenolog, suprastin, etc.) into the treatment scheme of the patient and to carry out several plasmapheresis displays. Treatment with F. is better to start immediately after finishing chemotherapy especially if lowering of immune-biochemical indices is revealed. If further reiteration of chemotherapy is supposed the treatment with F. is necessary to continue up to maximal improvement of immune-biochemical indices. One or two courses of F. in this case do not depend on the level of effectiveness, but on what biochemical indices are set after chemotherapy. Cancer is an immunological problem related with violation of antibodies formation as a responce to complex antigens of onco-associated proteins and remedies [8,13]. If immune-biochemical indices are evidently reduced than in this case the use of Plasmapheresis is an important addition to medical therapy. Also application of plasmapheresis is desirable after multiple courses of Poly-Chemotherapy (PCT). In this case the most informative to us is the definition of initial non-protein S-groups in blood serum. Their appearance is an evidence of Plasmapheresis necessity prescription. The use of F. between the courses of chemotherapy can replace the function of plasmapheresis. The application of F. between the courses of Chemotherapy can replace the function of Plasmapheresis, because F. has ability to have connection with immune complexes.
If after the mutual application of Chemotherapy and Flaraxin (F.) negative immune-biochemical indices appear (especially SH-groups) than the application of plasmapheresis is necessary. The number of Plasmapheresis corses can vary depending on the level of immune system violations (the control is the disappearance of SH-groups). So, for instance, under fractional plasmapheresis it is necessary to apply from 5 till 10 courses (with cleaning during each course up to 500 ml of blood). The prescription of F. strengthens chemotherapeutic effect and if endurance of the chemo-preparations applied is good, than reduction of its concentration is not desirable. Combination of F. and chemo- preparations in reduced doses is preferable in patients with accompanied diseases making massive chemotherapy application difficult. In heavy patients who got the prescription of F. it is necessary to reduce dose of chemo-preparations (1/5-1/10 of the normal dose) into the treatment scheme with the aim to strengthen oncologic activity of Flaraxin and also desirable to prescribe chemo-preparation that has never been used in this patient. The term of mutual application of F. and chemo-preparations must be defined by clinical picture and immunebiochemical indices of the patient. If each of these courses is accompanied by normalization of immune-biochemical indices, it is necessary to continue combination of Poly-Chemotherapy and F. 3-4 courses of F. can be considered as the ideal scheme, amplifying Chemotherapy and 1-2 courses of F. more in the following year after the end of Chemotherapy. It is also advisable to prescribe F. during the dispensary observation under disclosure of risk factors (stresses, reduction of immune-biochemical indices etc.) In the intervals between Chemotherapy when it is impossible to use F., phitopreparations of FITOMAX group are prescribed. Their mutual application is justified in these cases, when the application of the 1-st massive chemotherapy course is supposed. It was noted, that the use of preparations containing vegetative polyphenols and biological supplements with increased content of bio-flavonoids (silybrum mariarum, hellebores caucasicus, viola tricolor etc.) cause negative influence on therapeutic effect of F. (the studies are present). Probably in this case the level of Polyphenols chemical reaction with other components are playing main role (for instance, glychosylation). Clinically proved high efficiency of F. application in preoperative period. First of all, some decrease of tumoral nods is marked, which essentially simplifies the technique of operative intrusion; second, its powerful immunomodulatory and interferogenic properties allow to carry out surgical intrusion on good immunological background. Thus, the method of surgical treatment with preliminary application of 1-2 courses of F. therapy is clinically justified.
Accounting high anti-metastatic activity of F., it is advisable to carry out the treatment in post-operative period (1-2 courses of F.) as well as before application of chemotherapeutic preparations. In the cases when the use of chemotherapeutic preparations do not give positive results the application of F. is prescribed and able to give positive results. Clinically proved positive influence of F. on the patients: F improves general state; Tumoral nods became smaller or disappearing at all; F gives improvements to immunological indexes of immune system; F. increases vitality and movement activity; Reduces pain.
The efficiency of the Flaraxin is confirmed by: Kiev Medical Institute Department of Oncology, R.E.Kavetskyi Institute of Experimental Pathology, Oncology and Radio-biology of National Academy of Science of Ukraine Filatov Institute of eye diseases and tissue therapy AMS of Ukraine, Department of Oncology of Crimean State Medical University named after S.I.Georgiyevsky, Department of Oncology D. K. Zabolotny Institute of Microbiology and Virology of NAS of Ukraine.
FLARAXIN APPLICATION EFFICIENCY IN DIFFERENT CASES WITH CANCER.

Maximum, (***)
1. Melanoma;*** 2. Tumors of the mammary gland;*** 3. Tumor of lungs, little worse bronchi tumors;*** 5. Cancer of the colon;*** 6. Cancer of the rectum;*** 7. Cancer of the prostate gland;*** 8. Non-malignant tumors;*** 9. Adenoma; *** 10. The tumors of feminine sexual organs: *** 10 A) Fibromioma; *** 10 B) Cervix of the uterus Cancer; *** 10 C) Cancer of womb body; *** 10 D) non-malignant tumors of gonads, polycystic (calcined); *** 10 E) Cancer of gonads; *** 11. Tumors of CNS (Tumors of Cerebrum (Brain)): *** 11 A) Ependioma non-malignant; *** 11 B) Oligodendroglioma; *** 11 C) Astrocitoma; *** 11 D) Tumors of pituitary gland; *** 11 D1) Adenoma of pituitary gland; *** 11 D2) Carnofaringioma; *** 11 E) Brain metastases. ***
High, (**)
1Neoplasms of maxillofacial areas: Cancer of the lips, tongue cancer;** 2. Tumor of the upper respiratory tract and bodies; ** 3. Cancer of the maxillary sinus; ** 4. Tumor of the pharynx; ** 5. Tumor of the larynx; ** 6. Mediastinal tumors; ** 7. Tumors of the stomach; ** 8. Pancreatic cancer;** 9. Tumors of the kidney: adenocarcinoma ** 10. Bladder cancer. **
Average, (*)
1. Sarcoma of soft tissues of any etiology;* 2. Sarcoma of bone (depends on the blood supply to tumors); * 3. Tumors of the esophagus (at the last stage IV could only prolong life, but in the initial stages till III stage can be treated well); * 4. Metastases in Liver (liver cancer - is inefficient, but metastases to the liver - can be well treated); * 5. Tumors of the testis; * 6. Tumors of the penis. *
Non-efficient, (-)
1.Diseases of blood, leukemia, lymphogranulomatosis (immunosuppression should be done, and vice versa Flaraxin raises immunity); (-) 2. Extensive liver disease; (-) 3. Intoxication (moderate, high) are required to reduce the level of intoxication, because Flaraxin destroying tumor tissue and by this way increases the level of intoxication; (-) If you have high pain level. The work of Flaraxin is complicated and it can give more pain in the first days of application.
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TREATMENT SCHEME
FLARAXIN (intravenous injections) - 16 vials. The contents of the vial dissolved in 20 ml of 5% glucose or saline. Enter intravenously. Cones with FLARAXIN - 30 suppository. At 1 suppository in the vagina after mikroenema 1 time a day before going to sleep.
The scheme introduction: One intravenous infusion during 8 days; Time interval (break) 5-7 days; Again one intravenous infusion during 8 days; The break between infusion courses (between first course and second course) 10-14 days.
Table 1. The general scheme of application of preparations by the scheme. Medications Days 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
1 2 3 4 FLARAXIN injections Cones with FLARAXIN
- different variants
The scheme written by Elena Oleynik Doctor of the STCCC PHOENIX Tel: +380984805900 Fax: +380577056271 E-mail : stccc.phoenix.ua@gmail.com
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FLARAXIN Questions and answers
Professor, DMS A.V.Artyemov answers the questions (Filatov Institute of eye diseases and tissue therapy AMS of Ukraine, Department of Oncology)
1. What is Flaraxin? Flaraxin as a powerful specific and anti-tumoral interferonogenic medicine of vegetarian origin that is produced by unique technology. The acting substance of the medicine consists of vegetarian polyphenol compounds. Flaraxin is a lyophilized powder of yellow-brown color, well dissolved in 5% glucose solution, physiological solution and water. 2. Is Flaraxin administered for? Flaraxin is applicable for all clinic-morphological forms of malignant neoplasms, on all stages of tumoral process, nonmalignant neoplasms, under viral, inflectional diseases, accompanied with development of secondary immunodeficiency, inertial viral infections of CNS, diseases, characterized by the development of autoimmune aggression. 3. What is known about mechanism of Flaraxin action? Flaraxin has strictly expressed specific activity to oncological proteins in organism, causes micro-denatured changes in tumoral cells that causing their death with further elimination. Besides specific anti-tumoral effect of Flaraxin has an ability to activate production of endogenous interferon and the tumoral necrosis factor (TNF) in organism, F. able to support interferon high concentration during 72 hours after injection. This phenomenon provides wide participation of the immune system in the fight against tumoral structures. 4. What advantages has Flaraxin in comparison with traditional methods of treatment applied in oncology? Known treatment methods of oncological patients (chemotherapeutic, radiothrapy and surgical) that are accompanied by high immune suppression, closing vicious circle of tumoral process. The chemotherapy are using medicines, that have a number of reactionally-capable groupings and able to denaturate normal proteins (normal cells) with oncological protein groups, that explains its high toxicity for all body. Flaraxin associated only with tumoral cells (proteins), causing their death and it does not have influence on hematogenesis, on respiratory organs, on excretory and digestive systems, on CNS, on skin and others. Flaraxin is powerful immunomodulator that does not suppress immune system but vice versa raises its level of functional activity. 5. Can Flaraxin be used in patients with exposed allergy, bronchial asthma? Yes. Flaraxin able to associate and withdraw from the body the circulating immune complexes (CIC). Plasmapheresis is comparable with the ability of Flaraxin to remove CIC out of the body. The application of Flaraxin in patients that are suffering with allergic diseases, bronchial asthma essentially improves the state of patients in this category. 6. What is the advantage of FLARAXIN in treatment of infectious diseases in comparison with interferon groups? The injections of interferon (including those received by recombination) can give good clinical effect. But this therapy is passive, substitutive, that is giving already prepared interferon and as result the production of own interferon by the body will be reduced. Developed countries starts to use medicines that are able to stimulate production of endogen (personal) interferon and its essentially have influence on price of treatment methods as well as their effectiveness. Flaraxin is well combined with other preparations (antibiotics, sulfanilamides) and can be used in mono- and complex therapy.
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7. What kind of doses, ways and methods of treatment by Flaraxin exists? Flaraxin is produced in tree medical forms: ) lyophilized powder for intravenous injections 150 and 75 mg in glass bottles; b) Cones with flaraxin for rectal and vaginal application with 75mg of active substance c) Tablets and Capsules with Flaraxin for oral application with 75mg and 150mg of active substance. The application of Flaraxin in the dose 2 mg/kg for the patient is clinically confirmed. Whereas of absolute Flaraxin nontoxicity the twice- or thrice rising of the dosage does not have negative influence on the body. Normally Flaraxin is administered as 16 intravenous infusions for one course of the treatment. The injections of the Flaraxin can be done persistently (16 days, one injection a day) with 10-14 days break between the courses or it can be done by two half-courses each 8 days and than week break and again half-course 8 days by one injection a day. The break between the full treatment courses should be 10-14 days. It can be applicable with Cones, Capsules and tablets of Flaraxin rectally, vaginally or orally with aim to have local influence on tumors. The application of Cones is clinically justified under insufficiently exposed venous net or phlebitis, developed as a result of chemotherapy application. 8. What are side effects can be expected during Flaraxin application? During application of Flaraxin the allergic reaction can be marked very seldom, mainly its related with individual intolerance to iodine containing medicines. During treatment of oncological patients the light pain can appear in the main place of tumoral nod or metastases, more rarely the rise of body temperature up to subfebrile indices can be marked (37,0 38,5) as a response reaction of the organism on entering of tumoral cells decay products into the blood.
Professor, DMS A.V.Artyemov answers the questions (Filatov Institute of eye diseases and tissue therapy AMS of Ukraine, Department of Oncology)
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EXTRACT 1
from the report on clinical trial (the 1st PHASE) of a new anti-tumoral preparation Flaraxin Oncology Department of Kiev Medical Institute September 1990 to January 1991.
1. 2. 3.
Flaraxin in therapeutic doze (2 mg/kg) is non-toxic and is has good endurability by patients. Flaraxin can be injected in both ways: intravenously and intratumorally. Therapeutic effect of Flaraxin is registered in 100% of patients and is exposed by improvement of general state, reduction of neoplasm nodes size or their total regression. The most favorable results can be seen under prescription of Flaraxin on early stages of the disease and relapses. Flaraxin is a remedy of vegetable origin, it refers to non-toxic compounds, according to toxic estimation and clinical effect Flaraxin exceeds all known therapeutic anti-neoplasm remedies both native and foreign. Taking into account the results of clinical trial we consider it expedient to recommend Flaraxin for neoplasm treatment.
4. 5.
6.
Chair of the Commission, assistant professor of Oncology Department, Kiev Medical Institute
Doctor of Medical Science - I.P.Loboda.
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REPORT on the results of clinical trials of new anticancer drug FLARAXIN / 1 phase of research /
Research was conducted in the period from September 1990 till January, 1991 Oncology Department of P.L.Shupik National Medical Academy of Post-Graduate Education with Kyiv Oncology Dispensary Chairman of the Commission on the clinical investigation of FLARAXIN Chief of Oncology Department MD, prof. I.P.Loboda
Clinical Trial of the drug FLARAXIN in the treatment of melanoblastoma at different localization and stage. The goal of a clinical trial in melanoblastoma treatment was to determine the optimal clinical dose, duration of administration, treatment efficiency and toxicity evaluation of FLARAXIN. Study of FLARAXIN provided by Institute of pharmacology and toxicology Academy of Medical Sciences of Ukraine, based on the resolution of Pharmacological Commission of Ministry of Health of Ukraine on the I phase of clinical trials and instructions on it. During the study FLARAXIN we were guided by the methodological guidelines for the initial study of new antitumoral drugs approved by the Pharmacological Committee of Health Ministry of USSR (Moscow, 1975, page 84, 97). In the period until 15 June 1991 the staff of the Oncology Department of P.L.Shupik National Medical Academy of Post-Graduate Education (KMAPO) and First Hospice Department of the Kyiv Oncology Dispensary with consultation help of the author of FLARAXIN, medical oncologist of Kulik Ivan Anisimovich, have treated 30 patients with melanoma that diagnosis was histologically confirmed and is all of them was under observation. A list of patients presented in Table 1, compiled from Form 1 of guidelines for the initial testing of new anticancer drugs.
Treated 30 patients with melanoma and under supervision - are men and women aged from 27 to 77 years. Distribution of patients by age and sex is presented in Table 1. We watch for the dynamics of tumor growth by daily measurement of diameters of each tumor in three mutually perpendicular planes, with subsequent calculation of average tumor volume for each group in each period. FLARAXIN in therapeutic doses has no toxic effect on the blood and hematogenesis, liver, kidneys, CNS, lungs, gastrointestinal tract. Flaraxin toxicity to the current WHO estimate corresponds to 0 (zero). However, it should be noted that in patients previously treated with Poly-Chemio-Therapy (PCT), particularly in combination with radiation therapy, sometimes marked nausea and vomiting.
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List of patients with melanoma (I phase)

Name, Age, years 2 Primak .. 49 Khatunkina V.V. 52 Koshevich G.R. 56 Dzhunkovskiy .V. 54 Panchenko I. 58 The gen- Way of administeral condi- ration tion before treatment 3 4 5 6 female Melanoma of the 1 Intravenously left shin, operated in 1986 female Melanoma of the 3 left shin, Mts in the groin female Melanoma of the 3 intrascapular region male Melanoma of the 3 back skin, Mts in both axillary regions Melanoma of the 3 temporal region skin, Mts in lymph nodes of neck Sex Diagnosis Daily dose, Duration 7 2mg/kg Course duration 8 15 days Changes of Side effects Therapeutic results leukocytes and Objective Subjective and platelets complication 9 No marks 10 Till 8 injections more heaviness feels in body unnoticed 11 12 Full regression of Patient became tumor nodes active
Remission period after FLARAXIN 13 14 Alive from 1 08.1990
Intravenously 2 mg/kg
1 course 15days, 2 course 20days 21days
No marks
Full regression of Treatment endured Alive from 1, groin nodes and satisfactorily 10.02. tumor nodes 1991 Treatment endured Alive from 2 satisfactorily 20.02. 1991 Treatment endured Alive from satisfactorily 15.02. 1991 6 Treatment endured Alive from satisfactorily 18.02. 1991 8 (
Intravenously 1,8 mg/kg
Without changes No marks
18days
Left Vein Full regression of elbow Irrita- tumor nodes, tion brightening of first nidus unnoticed Regression of tumor more than 60% unnoticed Regression of tumor more than 60%
After 14days, surgery by 10 injecAfter opera- tions on 0,8 tion, 12days thousands interval, --------24days + stimulation additional on 1,5 after 1 month thousand with imbibition of tumor node 6 Kovalenko male Melanoma of the 3 Intravenously 2 mg/kg 1st course - No marks V.G. skin of left precos15days, 48 tal generalized after 3 --------form of Mts in weeks No marks lungs - - - - - - - - inflammation 2nd course reaction type 20days after and pain, 4 weeks + that disapintratumorally peared after 3 weeks 7 Pilipenko G.M. female Melanoma of the 3 Intravenously Done 3 flaraxin 15 days 3rd course of 40 skin (1st and 2nd courses + 5 without Flaraxin + course only Vincristine, in interval, Vincristie, flaraxin, dose 2 mg/kg break leukocytes 2nd-3rd 3 weeks, falling till 3 course with 20days thousand. Vincristine) injections, break, 1 month interval, 3 weeks, 20days+ Vincristine 8 Klininskiy K.I. male Melanoma of the 3 Intravenously 2 mg/kg 18 days + Leukocytes 68 back skin, Mts in surgery stimulation both axillary on 1 thouregions sand. 9 Basov V.N. male Melanoma of the 3 Intravenously 1,8 mg/kg 15 days + Leukocytes 52 back skin, Mts in surgery, stimulation both axillary additional on 5 thouregions course sand. 10 Lesnik G.V. 36 female Melanoma of 3 Intravenously 1st course leukocytes posterior triangle 4 mg/kg falling from 9 of neck, ------------till 5 thoulien and low 2nd course April sand maxillary 2 mg/kg --------abarthrosis Without changes
male
Intravenously 4 mg/kg 14 days, 2 mg/kg 12 days
unnoticed ------unnoticed
Full Regression of feeling of welltumor nodes and being. separate full regression In 3 nodes more than 50%
Alive from 1 20.12. 1990 1
Vein elbow Irritation on 3rd course of the treatment
Full Regression of neck node. After 2nd course operation
3rd course of Flar- Alive from axin + Vincristine 10.10.1990 19 gives bad feelings
unnoticed
unnoticed
Regression of Mts lymph nodes more than 60% + surgery Regression of Mts lymph nodes more than 60% Stabilization of the process -------Stabilization of the process
Feels without changes Feels without changes
Alive from 6 15.02.1991 Alive from 7 23.01.1991
unnoticed -------
Reduced pain in Alive from 7 joints 27.02.1997 ----disappeared pain in masticatory joint
16
11 Petrenko A.P. 41
male
Melanoma of 3 concha of auricle, Mts in lymph nodes of neck
Intravenously 2 mg/kg all quantity of Flaraxin was 3000 mg + surgery Intravenously 1,8 mg/kg
20 days + surgery
Without changes
Left Vein Regression of Treatment endured Alive from 6 elbow Irrita- tumor nodes more satisfactorily 6.10.1990 tion than 30%
12 Kozerog E.T. 71
male
13 Kuzmenko Y.V. 59
male
Melanoma of 3 napex skin, Mts in lymph nodes of neck Melanoma of 3 head skin, generalization of the process Melanoma of the 3 back, Mts in right axillary region, diabetes, heavy form Melanoma of hair 3 head part , Mts in shoulder girdle and lungs
17 days + surgery 20 days
Without changes
14 Boryak N.N. 52
male
Intravenously 2 mg/kg by 1 mg/kg in the morning and 1 mg/kg in the evening Intravenously 1st course 2 mg/kg -----2nd course 2 mg/kg Intravenously 1,5 mg/kg
20 days
Right Vein Regression of elbow Irrita- conglomerate tion nodes from 50% till 80% Increased unnoticed Regression of leukocytes tumor nodes more on 1,3 thouthan 60% sand thrombocyte Without unnoticed Disappeared changes initial spot Mts regression of tumor nodes more than 50% Without changes ------Without changes Increased leukocytes on 0,8 thousand Without changes unnoticed -----Right Vein elbow Irritation unnoticed
Treatment endured Alive from 3 satisfactorily 6.10.1990 Treatment endured Alive from satisfactorily 15.03.1991 5
Treatment endured Alive from satisfactorily 10.03.1991 . 4-
15 Gutsulyak P.V. male 32
20 days -----20 days 19 days + surgery 17 days
Disappeared pain Treatment endured Alive from in shoulder joint satisfactorily 04.09.1990 . ------10 . Regression of tumor nodes more than 40 %
16 Savicheva I.V. 35
female Melanoma of 3 femus skin, Mts in inguinal lymph nodes 17 Mogilnaya V.I. female Melanoma of right 2 39 shank skin, Mts in bones of skull and right lung female Diffusion Melanoma, relapse, after surgery of neck hem male 3
Regression of Treatment endured Alive from . tumor nodes more satisfactorily 17.02.1990 than 30 % 6 Reduced nodes on - liver (palpation) . . Alive from 1988 2
Intravenously 2 mg/kg by 1 mg/kg in the morning and 1 mg/kg in the evening Intravenously 1,8 mg/kg
unnoticed
18 Gorobets L.T. 52
20 days
Without changes
unnoticed
Brightening of Treatment endured Alive from 02.90 darck-cyanochroic satisfactorily 1.03.1991 region, reduced infiltration Regression of Treatment endured Alive from 7 tumor nodes from satisfactorily 20.02.1991 10sm*8sm till 8sm*6sm Reduced p/p nodes, revealed Treatment endured Alive from 12. 89. satisfactorily 17.04.1991
19 Yakushenko Y.N. 54
Melanoma of left 3 shank skin, Mts in lungs
20 days
Without changes
unnoticed
20 Rodionov A.V. 60
male
Melanoma of left 3 buttock with generalization of the process
27 days
Reduction of unnoticed leukocytes from 10 till 6 thousand Reduction of unnoticed leukocytes on 0,8 thousand No marks unnoticed
21 Kuhar A.T. 31
female Melanoma of the 3 back skin
Intravenously 2 mg/kg infiltration into tumor nodes Flaraxin Intravenously 2 mg/kg
15 days + 10 days
Big nodes reduced Treatment endured Alive from 11. 89. more than 50% satisfactorily 22.04.1991 3 full regression
22 Khilchevskaya female Melanoma of the 3 A.L. right axillary 65 region, Mts in lymph nodes female Melanoma of left 3 shank skin, Mts with generalization of the process
14 days
Regression of Mts Treatment endured Alive from 02. node satisfactorily 15.01.1991 90 .
23 Fedorchenko S.V., 27
Intravenously 2,3 mg/kg
14 days
Veins Irritation
Veins Irritation
Full regression of Treatment endured Alive from 12. 90. 3 nodes and satisfactorily 11.01.1991 reduction of others more than 50%
17
24 Lyahovskaya N.P., 52
25 Dobrenko M.I. 43
female Melanoma of 3 straight intestine, Mts in pelvis bones female Melanoma of 3 mammary gland skin, Mts in lymph nodes of axillary regions male Melanoma of the 3 righ lobe of the ear
20 days
unnoticed
unnoticed
Regression of Treatment endured Alive from 5 tumor on anus on satisfactorily 15.05.1991 2/3 Treatment endured Alive from 11 satisfactorily 28.02.1991 90 .
26 Kostenko A.G. 40
Intravenously After surgery, preliminary histological conclusion (PGC): Mts in lymph nodes 2 mg/kg Intravenously After surgery, PGC: Mts in lymph nodes 2 mg/kg
16 days + unnoticed Prophylactic course
unnoticed
1*20 days unnoticed after 3weeks 2 mg/kg 15 days
unnoticed
Alive from 2 . 20.02.1991
27 Gorbunova N.I. 34
female Melanoma of the 3 left thigh female Melanoma of left 3 shank female Melanoma of neck 3
28 Stepanenko G.I. 27
29 Maslovskaya N.V. 31
Intravenously A/s PGC: Mts in 21 days unnoticed lymph nodes + 1,5mg/kg Prophylactic course Intravenously A/s PGC: Mts in 10 days unnoticed lymph nodes + 2 mg/kg Prophylactic course Intravenously A/s PGC: Mts in 10 days unnoticed lymph nodes 2 + mg/kg Prophylactic course Intravenously A/s PGC: Mts in 10 days unnoticed lymph nodes + 2 mg/kg Prophylactic course
unnoticed
. . .
Alive from 12. 90. 17.05.1991 Alive from 02 7.02.1991 90. Alive from 0. 90. 17.05.1991
unnoticed
unnoticed
30 Momitko S.I. 36
female Melanoma of mammary gland skin
unnoticed
Alive from . 04.04.1991 04
Table 2. Distribution of patients by sex and age. Age (years) Total 20-29 30-39 40-49 50-59 60-69 70-79 Male 6 3 4 2 1 16 Female 2 3 2 4 2 1 14 Sex
The efficiency of melanoblastoma treatment by Flaraxin The criterion for the effectiveness of patients treatment with melanoma by FLARAXIN was the regression rate of tumor nodules and changes in well-being of patients. It should be noted 100% effectiveness of melanoma treatment, but its severity varies. Significantly lower the effectiveness of treatment in patients with disseminated forms melanoma. At first FLARAXIN received only patients with generalized forms of melanomas or with metastases to vital organs. After confirmation in the anti-melanoma efficiency of FLARAXIN expressed in partial regression of tumor nodes and improved well-being of patients, we started to treat less inveterate cases. It was marked the loss of efficiency in the melanoma treatment after previously treated patients by PCTs and radiotherapy and better improvement of the melanoma treatment was seen in cases of PCTs and Radiotherapy absence. The distribution of patients with recurrent melanoma who previously received mono- or combination therapy (not earlier than 3 months before FLARAXIN treatment) is presented in Table. 3. Table 3. The distribution of patients with recurrent melanoma of the groups that received earlier mono- or combined conventional (PCTs or radiotherapy) therapy (not earlier than 3 months before FLARAXIN treatment). Table 3 Treatment done Surgery Surgery only by Flaraxin treatment treatment + PCTs 3 no 13 6 10 5 Surgery treatment + PCTs + Radiotherapy 5 2
Patients quantity Patients with recurrence after
18
During treatment FLARAXIN observed dependence of efficiency on the duration of the disease, primary or recurrent melanoma. Comparative evaluation is presented in Table. 4. Table 4. The efficiency of FLARAXIN treatment at various periods of melanoma growth. Periods of till From 2 More than disease 2 month till 6 month. 6 month Treatment 100% till 50% More than till 50% More than result ,% 50% 50% Quantity of 3 6 4 9 2 treated patient's Noteworthy are initially FLARAXIN treated patients: Patient B., 52 years old Diagnosis: melanoma in interscapular region, Metastases in the right axillary region. He has diabetes, severe disease, post infarction myo-cardio-sclerosis. Treated with fractional doses of 1 mg/kg in the morning and in the evening during 20 days (FLARAXIN dissolved in physiologic solution). The diagnosis was confirmed by the results of axillary node biopsy for 1 month before treatment FLARAXIN. Melanoma spot of interscapular region disappeared, leaving the surrounding satellites that have adopted a more intense color. Metastatic axillary node was reduced by 50%. The stabilization process was observed for 2 months. A second course of FLARAXIN treatment helds in conjunction with 2 infusions of Vincristine. Patient K., aged 56. D-s: melanoma of the skin back, axillary lymph node metastases in the region (in the center melanoma spot keratinous region with size of 2.5 cm x 3cm x 3cm). He/She was treated by FLARAXIN during 20 days at a dose of 2 mg/kg daily. After the treatment was determined complete regression of metastatic axillary node and enlightenment of melanoma spots. Keratinous region was removed by surgery operation. The application of Vincristine on the background of the FLARAXIN treatment Patient P., 40 years. D-s: melanoma of right shin. Operation in 1989, recurrent metastases in the neck, in juxtaspinal chest and in right inguinal region. Large tumor nodes up to 12cm in diameter. From 10.10.90 till January 1991 received 2 FLARAXIN courses in daily dose of 2 mg/kg and every course duration was 20 days. Cervical node complete regression as a result of treatment and on his back and groin nodes decreased by 1/3. 3rd course was carried out in combination with surgery. After 10 days of FLARAXIN treatment was performed excision of the remaining nodes and subsequent 8 infusions of FLARAXIN combined with the injections of "Vincristine" 4 times. In February, the patient was observed alopecia, at 3 months after treatment appeared recurrent disease node in the right groin. In the node introduced 0,2% solution FLARAXIN. In the node region appeared swelling and pain, which disappeared in 3 days. Internodes infiltration was used in 4 cases in parallel of intravenous infusions of FLARAXIN; initially, there was an increase in reactive nodes and pain, then these events took place and nodes decreased to its original size. Two patients came during the generalization process. In the first 10 days of new nodules appeared during treatment of FLARAXIN. Application method of FLARAXIN and optimal therapeutic doses Ascertain that no toxic effects was observed after 20 infusions of FLARAXIN at a dose of 2 mg/kg in cases where not obtained complete regression, we increase the number of injections till 30. In two cases with intratumoural infiltration and intravenous infusions of FLARAXIN, there is persistent stabilization of the melanoma process. The post-operative treatment after FLARAXIN course with partial regression of nodes remains unresolved. It seems inexpedient to do operation, because FLARAXIN treatment, in our opinion, has more prolonged remission than with surgical interventions. The application of Flaraxin doses above 2 mg/kg a day is not advisable, because at a dose of 4 mg/kg a day during 15 days reduction of 10-15% of hemoglobin and leukocyte counts, whereas in the average daily dose of 2 mg/kg partly stimulates hematopoiesis and regression of tumors is identical. In addition, a dose of 4 mg/kg causes some nausea and discomfort in patients. It is known that chemotherapy of melanoblastoma, both independently and in combination with radiation therapy and surgical intervention, are not effective. In connection with this melanoblastoma treatment remedies is urgent actual task in modern medicine.
19
Conclusions
1. FLARAXIN interacts with human serum albumin (HSA) and cytochrome-C with the participation of tyrosine and tryptophan residues. Application of 5% glucose able in order to inhibit the reaction of HSA with FLARAXIN, and contributes in increase of the interaction speed with tyrosine and inhibit the interaction with tryptophan residues. 2. Acute toxicity of FLARAXIN when injected intravenously into rats is 4-5 times less than those in base substance of FLARAXIN. 3. FLARAXIN is little cumulating substance and does not alter body weight, liver and spleen of mice.
4. FLARAXIN has an antioxidant effect that is manifested by increased survival of animals poisoned with carbon tetrachloride. Antioxidant properties of FLARAXIN in vitro are more significant in comparison with alfatocopherol. 5. FLARAXIN in dose of 10 mg/kg intramuscularly, within 6-15 days before immunization does not have adversely impact on the humoral and cellular immune reactivity of the body. 6. Pronounced signs of FLARAXIN overdose in experiment on dogs occur when doses of the drug was 40 times higher than daily therapeutic dose 2mg/kg. For the treatment of such poisoning is necessary to use a set of drugs that have a positive effect on tissue respiration (nicotinamide), vessels (calcium gluconate), with antihistaminic action (diphenhydramine). 7. In intravenous administration of FLARAXIN to the rats actively distributed in the animal body (volume of distribution in the blood plasma is 3.40 L/kg). The maximum concentration of FLARAXIN drug in the organs and tissues of animals is determined at 1 hour after injection and higher on 75-178% than in blood plasma, equal to 9.19 mg/liter. FLARAXIN is able to circulate long period in the blood plasma of animals - period of half elimination is equal to 5,8 hours. The main way of FLARAXIN excretion and/or its metabolites from the organism of animals is with help of kidneys. 8. Developed Temporary Pharmacological Article (TPA) on FLARAXIN and laboratory-technological rules.
9. Treatment of 30 patients with melanoma by FLARAXIN in a daily dose of 2 mg/kg was effective in most cases. In this dose of the FLARAXIN drug has no negative effect on the blood, central and peripheral nervous system, CAS, respiration, liver and kidney function. Stable remission with complete regression of melanoma nodes was observed mainly on the earlier 3rd stages and partly on the 4th stage of cancer. Treatment of the extensive forms of melanoblastoma by FLARAXIN can be combined with Vincristine and FLARAXIN can be infiltrated directly in tumor nodes.
Research was conducted in the period from September 1990 till January, 1991 Oncology Department of P.L.Shupik National Medical Academy of Post-Graduate Education with Kyiv Oncology Dispensary Chairman of the Commission on the clinical investigation of FLARAXIN Chief of Oncology Department MD, prof. I.P.Loboda
20
EXTRACT 2
from the report on clinical trial of a new anti-tumoral preparation Flaraxin on 10 patients with melanoblastomas (the 2nd PHASE)
R.E.Kavetskyi Institute of Experimental Pathology, Oncology and Radio-biology of National Academy of Science of Ukraine Kiev From December 1992 to October, 30, 1993.
1.
Flaraxin in daily doze 2 mg/kg under intravenous injection during up to 20 days show no toxic influence on central and peripheral nervous system, vital organs, blood and hematopoiesis. Therapeutic effect of Flaraxin under melanoblastoma forms in a state of neglect depends on term of disease, character and stage of inner organs affection. It becomes apparent by the improvement of patients state, stability of process, regression of neoplasm nodes in average up to 50%. To recommend to Pharmacological Committee of Ukraine to allow clinical application of the preparation Flaraxin for melanoblastoma treatment.
2.
3.
Chair of the Commission on clinical trial of Flaraxin, Chief of the scientific-research department of head and neck neoplasms and modified methods of treatment
Doctor of Medical Science - V.S.Protsick.
21
Report the result of clinical trial of new anticancer drug FLARAXIN / 2 phase of reseach /
R.E.Kavetskyi Institute of Experimantal Pathology, Oncology and Radio-biology of National Academy of Science of Ukraine Kyiv Approved: Director of Kiev SRI of Eperimental pathology, oncology and Radio-biology MD, Prof. - S.A.Shalimov Chairman of the Commission on the clinical investigation of FLARAXIN Chief of Scientific Research Department of head and neck tumors and modified treatmen methods MD, prof. V.S.Protsyk
It is known that chemotherapy of melanoblastoma, both independently and in combination with radiation therapy and surgical intervention, are not effective. In connection with this melanoblastoma treatment remedies is urgent actual task in modern medicine. In the 2nd phase of clinical trials we studied the therapeutic effect FLARAXIN in patients on the last stages of malignant melanomas. Totally 10 patients were treated with 4 stage of the disease in the period from December 1992 till 30 October 1993. All patients diagnosed with melanoma were confirmed by histological examination . FLARAXIN treatment was carried out in accordance with the recommendation of the pharmacological committee. The contents of the vial, 150mg lyophilized powder of FLARAXIN, dissolved in 20 ml of 5% sol. glucose and injected intravenously, simultaneously, 1 time a day. The course of treatment - 20 intravenous infusions. We studied the toxic influence of FLARAXIN and its efficiency /rate and duration of remissions/ on patients. During clinical trials it was noted that FLARAXIN has no negative effect on the function of the central and peripheral nervous system, cardiovascular system, liver, kidney, gastrointestinal tract, does not affect the morphological composition of blood and hematopoiesis. FLARAXIN toxicity equals zero by WHO estimation ("antineoplastic therapy" Moscow, J.Medicine, 1986, s.166). FLARAXIN efficiency was clearly seen in all 10 patients on the last stage of melanoblastoma. There is a direct correlation of therapeutic effect with illness duration - the sooner treatment was started, more high therapeutic effect will be seen. There is improvement in general condition, regression of tumor nodules up to 30-40%, the stabilization process and remission were over 6 months. (See Table.1). In very difficult cases the effect of FLARAXIN treatment was negligible. With metastases in the lungs, liver and other vital organs was noted only the improvement of general condition, reduction of tumor nodules up to 15%.
22
Table 1. List of patients with melanoma (II phase). / 1 Name, Story Number 2 Vasilchenko Ludmila Nikolaevna story.4808/92 Skurchinskaya Lidia Nikolaevna story.0369/92 Sex, Age, years 3 female 52 female 62 The general Way of condition administbefore ration treatment 4 5 6 Melanoma of the Pain in Intraneck skin with Mts nodes venously in the lymph nodes Melanoma of the Pain and itch Intraforehead skin with in lymph venously Mts in the lymph nodes nodes of parotid region, 4 clinical group Melanoma of the Pain in the Intraeyebrow region eyebrow venously with Mts in the region gnathic lymph nodes 4 clinical group Melanoma of the Pain in the Intraparotid skin with parotid venously Mts in the neck region nodes 4 clinical group Melanoma of the Pain in the Intraoccipital region tumor nodes venously with Mts in the lymph nodes of neck 3 clinical group Melanoma of the Pain in the Intrahead skin with Mts tumor nodes venously in lymph nodes of neck 4 clinical group Melanoma of the Pain in the Intraface skin with Mts tumor nodes venously in lymph nodes of the neck 4 clinical group Melanoma of the Pain in the Intraface skin with Mts tumor nodes venously in lymph nodes of the neck 4 clinical group Melanoma of the Weakness Intrahead skin with Mts Cough venously in lungs 4 clinical group Melanoma of the Weakness Intraocciput skin with Pain in venously Mts in liver stomach Diagnos Daily dose Course Changes of Side effects duration leukocytes and complications 9 No 10 No Therapeutic results Remission period Objective Subjective after FLARAXIN 11 12 13 25% reduction No pain Alive from 08.03.93 of nodes anymore 50% reduction No pain Alive from 11.01.93 of tumor anymore nodes
7 8 2 mg/kg 20 vials, 20 days 2 mg/kg 20 vials, 20 days
No
No
Zignel Galina Vasilievna story913/92
female 43
2 mg/kg 20 vials, 20 days
No
No
regression of No pain Alive from 13.01.93 tumor nodules anymore more than 50% regression of No pain Alive from 09.02.93 tumor nodules anymore by 50% reduction of nodes more than 40% No pain Alive from 10.02.93 anymore
Salnikova Olga Alexandrovna story 507/92 Yatsenko Alexandra Alexeevna story 786/92
female 23
No
No
female 42
No
No
Grivkovskaya Ludmila Silvestrovna story 6574/92 Shedrina Tatiana Nikolaevna story 1352/92 Leykin Ivan Vasilievich story.1273/92
female 69
No
No
reduction of nodes more than 60% reduction of tumor more 50%
No pain Alive from 29.03.93 anymore
female 40
No
No
No pain Alive from 18.02.93 anymore
male 52
No
No
regression of No pain Alive from 03.01.93 tumor more anymore 45% Improvement of overall condition Improvement of overall condition 12.02.93 died after 2,5 month of the end of the treatment 09.01.93 died after 1,5 month of the end of the therapy course
Vorobey Leonid Timopheevich story 1050/92
male 52 female 26
2 mg/kg 20 vials, 20 days 2 mg/kg 20 vials, 20 days
No
No
10 Mogilnaya Valentina Ivanovna story 0967/92
No
No
23
REPORT on the results of clinical trials of new anticancer drug FLARAXIN /2 extended phase of research/
Oncology Department of Crimea State Medical University named after S. I. Georgievsky Simferopol 2001 Research was conducted in the period from May 1998 till September 2000. Executors: Chief of the III Oncological Department (mammary gland cancer) of CSMU d.m.s, professor A.G.Filenko Chief of the Radiological Department (cervical cancer) of CSMU d.m.s., professor N.I.Verizhnikova Chief of the II Oncological Department (melanoblastoma) of CSMU d.m.s., professor I.V.Pohvalin Rector: of the Crimea State Medical University (CSMU) named after S. I. Georgievsky MD, professor - A.A.Babanin Leader: Chairman of the Oncology Department of the Crimea State Medical University (CSMU) named after S. I. Georgievsky MD, professor V.M.Efetov Responsible Executor: Assistant of the Oncology Department (lungs cancer) of CSMU named after S.I.Georgievsky d.m.s, professor A.V.Protsenko Summary Report about Clinical Trial of comparable treatment efficiency and tolerance of the FLARAXIN drug produced by Scientific and Treatment Center for Cancer Curing PHOENIX Ltd. with base therapy and written on 30 pages of typed document and contains 6 tables and 43 sources of literature. The drug "FLARAXIN" is a light yellow or brownish-yellow lyophilized powder or porous mass, the following composition (active substance in the vial to 0,15 g): a based substance for FLARAXIN from 0,10 to 0,11 and the other components of 0,03 to 0,05. According to preclinical studies of the drug was found that "FLARAXIN" is a remedy of plant origin active components of which are plant Polyphenols. The study found that "FLARAXIN" has the ability to stimulate endogenous interferon and tumor necrosis factor contributes to the normalization of the immunological background and equalizes the ratio of immunocompetent cells CD4/CD8 (helper-suppressor) and increases the number of natural killer (NK-cells). During accomplishment of immuno-biochemical studies has been established the ability of "FLARAXIN" to bound onco-fetal proteins, causing their micro-denaturation damage. Carcinostatic effect is explained by the influence of "FLARAXIN" on the metabolism of tumor cells, causing their death. Based on these preclinical and Phase II clinical trial of the drug "FLARAXIN" we can conclude that it belongs to a group of almost harmless and non-toxic drugs, and does not have allergic and locally irritating effect, except cases of individual hypersensitivity to the drug "FLARAXIN". The study was conducted on 304 patients - with lung cancer stages III and IV; Breast Cancer II, III and IV stage, cervical cancer I, II, III, IV stage, melanoma. Accomplished clinical and bacteriological studies have shown that the drug "FLARAXIN, used intravenously, has significant antitumor, immunomodulating, and antioxidant action, thereby significantly affecting the quality and thus increasing life expectancy of cancer patients, especially in the early stages - I, II, III and some cases of IV stages of cancer process. There was no case of intolerance to the drug FLARAXIN.
24
Content of the Report 1. Ethical and legal standards of research; instruction of the patients; 1.1. Researchers and administrative structure of the study (the characteristic of clinical database). 2. Introduction 2.1. Ground of the study. 2.1.1. Theoretical assumptions 2.1.2. Experimental data and preliminary clinical study of the drug. 2.2. The Aim and objectives of the study. The overall study design. 3.1. Type of the study. 3.2. General description of the study. 3.3. Stages of the study. The investigated drug: 4.1. General characteristics of FLARAXIN; 4.2. Comparison with the basic therapy. Selection of the patients for the study: rationale formed comparison of groups, criteria for inclusion of patients and control group. Scheme investigation of the patients. 6.1. Investigation Methods of patients general status, Criteria for the evaluation of Cancer process flow Methods 7.1. 7.2. 7.3. of treatment. Data on previous treatment of patients The main treatment by the investigated drug; Concomitant therapy.
Criteria for evaluation of the treatment efficiency and tolerability of the drug. 8.1. Clinical and laboratory parameters of the Cancer process changes 8.2. Criteria for the evaluation of patient general state in dynamics. Evaluation of the treatment efficiency. 9.1. General characteristics of patients in groups; 9.2. Evaluation of the direction flow for the Cancer process 9.3. Dynamics of the patients general condition index in experimental and control groups. 10. Evaluation of the experimental drug Flaraxin on tolerability, on allergic and local irritating action, on (toxic) reactions. Discussion of the results and main conclusions. The list of literature. 1. Ethical and legal standards of research; instruction of the patients. This clinical trial was conducted in accordance with the Law of Ukraine "On Medicines", p.7, 8, and the principles of the Helsinki Declaration. This study was initiated after the approval of the clinical trial protocol by the Commission on the Ethics of the Pharmacological Committee of Health Ministry of Ukraine. Patients who are potential participants in the trial were informed about the character of clinical trials, investigated drug, as well as the possible risk associated with drug intake by "information sheet for the patients". All patients included in the study signed a written agreement with aim to participate in clinical trial. All documentation related to the study, as well as information concerning the patients who participated in the clinical trial are strictly confidential. 1.1. Researchers and administrative structure of the study (the characteristic of clinical database).
general and side
The General Executor - Crimea State Medical University named after S. I. Georgievsky, Simferopol (Rector prof. Academician Babanin A.A.) Address: 5/7 Boulevard Lenin, 95006-Simferopol, Crimea, Ukraine. Phone: +38-067-6433202 Fax: +38-064-2504908 Department of Oncology - (Chairman of the Oncology Department - MD, Professor Efetov V.M.) on the basis of the Crimean Republican Clinical Oncology Dispensary Address: 49a Bespalova st., Simferopol, Crimea, Ukraine. Tel: +38 0652 23-23-78 - Department +38 0652 23-23-72 - office +38 0652 25-57-35 - home
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Crimean Republican Clinical Cancer Center presented many oncology departments: I-Gynecological Department, II-Surgery, III-Chemotherapeutic Department IV-Proctologic Department V-Thoracic Department VI-Radiology Department VII-Hematological Department The clinic has cabinets ultrasound, gastroscopy, bronchoscopy, radiological investigations and laboratory - clinical, biochemical, bacteriological, histological and pathologic-morphological. 2. Introduction. 2.1. Ground of the study. At the present level of medical science development still remain topical issues of cancer treatment. Statistics in recent years shows that in developed countries the diagnosis of cancer "or" malignant neoplasm" is placed around one in three people over their lifetime, and about one in four dying because of cancer. As a result of the Chernobyl disaster that happened 26 April 1986 in extended territories of Ukraine, Belarus and Russia was created conditions of permanent contamination of the environment with wide range of radionuclides, that are continuing to came, till this days, to the human body with food, water and breathable air. The most serious of all consequences of radiation exposure on the human organism is cancer. Based on years of experience, using the available observations over large continents (about a hundred thousand people), survivors of the atomic bombings of Hiroshima and Nagasaki in 1945, showed that cancer was the sole cause of mortality in this population. Domestic authors note that patients with chronic, primarily domestic and short-term external exposure is increased the number of leukemia and stomach cancer, to a lesser extent - a tumor of urinary tract, brain, esophagus, cervix. The duration of a clear manifestation of the radiation effect of the tumor was found to be approximately 25-30 years. Note that ionizing radiation can also have influence on the potential tumor cells, i.e., on those cells that can be a source for malignant tumors, contributing to the degeneration of these cells and the development of cancer diseases. 2.1.1. The theoretical assumptions. It is known that treatment of tumors, despite to the enormous long-term efforts of scientists around the world, still remains largely unsolved problem. The Used methods, among which are essential, along with surgery is chemotherapy, alone or in combination with radiotherapy and radiotherapy, are often not sufficiently effective. In addition, all these effects by themselves cause immunosuppression, which leads to suppression of the medullary hematopoiesis and infectious complications, as well as the development of intestinal dysbiosis. As a result of tumor development the immune system is going down and radiation is another extra stroke that suppressing its activity. It follows thence that successful treatment of tumors may depend on the balance between antitumor efficiency of chemotherapeutic drugs and the potential of the immune system, adequate (or inadequate) to cope with the remaining amount of tumor cells that stays after the treatment. The foregoing leaves no doubt that the immune system is in the Centrum of the ongoing attempts to improve the efficiency of anticancer therapy, and main task is to activate the antitumor potential of the immune system and this is the most important task in modern oncology. Therefore, any attempt to weaken the side (immunosuppressive) effects of chemotherapy and Radiotherapy are unquestionably valid. 2.1.2. Experimental data and preliminary clinical study of the drug. Taking into account information on STCCC "Phoenix", Flaraxin drug was developed, which is a remedy of plant origin with active components of plant Polyphenols. The ability of FLARAXIN to stimulate endogenous interferon and tumor necrosis factor was proved, also FLARAXIN contributes to the normalization of the immunological background and equalizes the ratio of immunocompetent cells CD4/CD8 (helper-suppressor) and increases the number of natural killer (NK-cells). After FLARAXIN injection by the immuno-bio-chemical research has been find out that drug has ability to bind with oncofetal proteins, causing their micro denaturation damage. Carcinostatic effect is explained by the FLARAXIN influence on the metabolism of tumor cells, causing their death. 2.2. The Aim and objectives of the study. The aim of this study - a clinical trial on comparative efficiency and tolerability of FLARAXIN, lyophilized powder, the production company of STCCC "Phoenix" for cancer treatment. Tasks of the study: 1. To evaluate the antitumor effect of the drug "FLARAXIN in patients with breast cancer, cervical cancer, lung cancer and melanoma; 2. To conduct the comparative evaluation of clinical efficiency of "FLARAXIN" produced by STCCC "Phoenix" and the basic therapy; 3. To assess the tolerability of "FLARAXIN"; 4. Identify the possible adverse effect of the drug "FLARAXIN" on clinical and laboratory indices.
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3. General characteristics of FLARAXIN. Type of research. General description of research. Stages of research. An open randomized comparative study of the II extended phase of clinical trial of the drug "FLARAXIN" was carry out. The study was conducted on 300 patients, undergoing at a hospital treatment and the appropriate criteria of inclusion/exclusion was taken in to account and will be listed below. The relevant criteria for inclusion in the trial (development) patients give written consent to participate after referring and singing "information sheet for patients". Randomized distribution of patients participated in the clinical trial of the main (210 patients) and control (90 patients) groups performed using the method of random numbers. Prescription of the drug, timing interval and method of its application, the character of the concurrent therapy, clinical and laboratory data for monitoring the effectiveness and tolerability of the drug were evaluated on the proposed scale, statistically analysed for a comparative evaluation of treatment of investigated and control groups. 4. The investigated drug: general characteristics of FLARAXIN; Comparison with the basic therapy. The experimental drug is "FLARAXIN" produced by STCCC "Phoenix" Ltd, Kharkov. As a comparative therapy was used radiation therapy and chemotherapeutic drugs therapy. Content of the drug Flaraxin Base substance of "FLARAXIN" Other components of FLARAXIN 75% 25% 0,1125 g 0, 0375 g
The choice of comparative treatment justified: radiation therapy and chemotherapeutic drugs therapy is comparable with investigated drug on the effect on the life quality and life duration of cancer patients. 5. Selection of the patients for the study. Rationale formed comparison of groups, criteria for inclusion of patients and control group. Selection of the patients accordingly to the requirements of the Protocol on Clinical trials based on inclusion/exclusion criteria in the groups under investigation. Inclusion criteria Men and women; Age of patients: from 18 till 80 years; Patients with the cancer presence; Patient consent; Adequate patients ability to cooperate during treatment process; Exclusion criteria Hypersensitivity to various drugs in the anamnesis; Related decompensated diseases or acute condition, the presence of which can significantly affect the results of the trial; Patients inability to refuse from application of alcohol and/or drugs during treatment; Participation in any other clinical trial; Patients inability to adequately cooperate with the doctor in the research process; Criteria for patient quit Individual intolerance; The appearance of heavy and/or unexpected adverse events of the patient in the study; Significant deterioration in general condition during the study period; Regime failure of the appointed drug; Refusal of a patient from participation in the study; 6. Investigation scheme of the patients. During Trial for the patients included in the test, was conducted a inspection using clinical, laboratory and instrumental methods for the following parameters, in accordance with the diagnosis of the disease: 6.1. Investigation Methods of patients general status, Criteria for the evaluation of Cancer process flow. Before and after end of the treatment course: An objective examination (examination: percussion, palpation, auscultation, general weakness, decreased performance, presence and severity of pain); Subjective assessment of well-being of patients; Histological examination of the tumor; X-ray examination; Complete blood analysis (hemoglobin, erythrocytes, leukocytes, platelets, wbc, color index, ESR); Clinical analysis of Urine (amount, pH, specific weight, leukocytes, erythrocytes, cylinders, epithelial cells, salts, mucus). Additionally, special methods of investigation were: for lung cancer - bronchoscopy, for cervical cancer - colposcopy, for breast cancer - an additional X-rays (mammography), for melanoma - X-ray examination was carried out.
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7. Methods of treatment, data on previous treatment of patients, the main treatment by the investigated drug, concomitant therapy. Prior treatment of cancer was evaluated with account on characteristics of the methods and forms used drugs and timing periods of their application, as well as the effectiveness of treatment. Drug under investigation Patients of all experimental groups received the investigational drug "FLARAXIN" by simultaneous injection 1 times a day, in a dose of 2 mg/kg patient's weight, the contents of the vial (150 mg powder FLARAXIN) was dissolved by physiological solution during 16 days - 1 course of treatment, maximum was recommended - III courses of "Flaraxin". The interval between courses was 30 days. Comparative base therapy Patients of the control group received basic anticancer therapy in accordance with their diagnoses (chemotherapy or radiation therapy for individual indications). The additional treatment. Interaction with other drugs. During the investigation permitted the appointment of medicines used to treat primary and related diseases, based on the etiology of the disease and condition of the patient, doctor could appointed additionally metabolic, vitamin and other medicines. All drugs used for concomitant therapy, were marked, including name, dose, method of admission, frequency of admission, date of commencement and completion of therapy, in the history of the disease and the individual registration form (Annex 1). 8. Criteria for evaluation of the treatment efficiency and tolerability of the drug. Evaluation of the treatment efficiency was based on the dynamics of the cancer process, as well as directional changes in the general condition of patients during treatment. Antitumor effect of Flaraxin was indicated by the disappearance or reduction of the severity of clinical indications of tumor process: reduction of the pain, improvement of general well-being, improved appetite, visual or palpation examination - a reduction or cessation of tumor growth, x-ray evidence of regression or stabilization of cancer process. Table 1. The examination scheme of patients major groups. Investigated indexes Examination period Before After treatment I course 1 Patients conformity evaluation by the criteria for patient inclusion in the trial Obtaining written informed consent from patient Anamnesis Objective examination Registration of subjective patient complaints Histologic examination X-ray examination Complete blood analysis Clinical analysis of urine Registration of side effects Control for compliance with treatment Evaluation of efficiency Evaluation of tolerability Table 2. Distribution of patients by age. Age, years 21-30 Groups Absp. % Lung Cancer Experimental group (n=50) Control group (n=20) Mammary Gland Cancer Experimental group (n=40) Control group (n=20) Cervical Cancer Experimental group (n=60) Control group (n=25) Melanoma Experimental group 2 3,3 (n=60) Control group (n=25) 2 8,0 2 3
Before II course 4
After II course 5
Before III course 6
After III course 7
31-40 Absp. 3 1 2 1 5 3 3 1
% 6,0 5,0 5,0 5,0 8,3 12,0 5,0 4,0
41-50 Absp. 5 2 10 8 7 2 13 4
% 10,0 10,0 25,0 40,0 11,7 8,0 21,7 16,0
51-60 Absp. 18 13 12 7 11 8 7 11
% 36,0 65,0 30,0 35,0 18,3 32,0 11,7 44,0
61-70 Absp. 24 4 16 4 24 7 21 5
% 48,0 20,0 40,0 20,0 40,0 28,0 35,0 20,0
71-80 Absp. 13 5 14 2
% 21,7 20,0 23,3 8,0
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Table 3. Distribution of patients by sex. Sex Groups Men Abs. persons Lung Cancer Experimental group (n=50) 38 Control group (n=20) 11 Melanoma Experimental group (n=60) 14 Control group (n=25) 12
% 76 55 23,3 48
Women Abs. persons 12 9 46 13
% 24 45 76,7 52
8.1. Clinical and laboratory parameters of the Cancer process changes. Criteria for evaluating the efficiency of the drug Flaraxin in the treatment of lung cancer: 1. Clinical data:
The disappearance or reduction of the severity of subjective symptoms of antitumor process: improvement of general health, the appearance of appetite, normalization of mental and emotional status. The disappearance or reduction of the severity of objective indexes of antitumor process: Cough, sputum production, decrease of pain, and normalization of respiratory function. 2. Laboratory data:
The positive dynamics of laboratory parameters: X-ray of the lungs - with stabilization or reduction the tumor progression, improvement of laboratory parameters during bronchoscopy. Criteria for evaluating the efficiency of the drug Flaraxin in the treatment of cervical cancer: 1. Clinical data:
The disappearance or reduction of the severity of subjective symptoms of antitumor process: improvement of general health, the appearance of appetite, normalization of mental and emotional status. The disappearance or reduction of the severity of objective indexes of antitumor process: reduction of excrements from the genital tracts (watery or blood character), reduction of pain syndrome, normalization of physiological functions of urination, defecation. 2. Laboratory data:
The positive dynamics of laboratory parameters: pelvic radiographs - stabilization or reduction of tumor progression, improvement of laboratory dynamics during colposcopy. Criteria for evaluating the efficiency of the drug Flaraxin in the treatment of mammary gland cancer: 1. Clinical data:
The disappearance or reduction of the severity of subjective symptoms of antitumor process: improvement of general health, the appearance of appetite, normalization of mental and emotional status. The disappearance or reduction of the severity of objective symptoms of antitumor process: reduction of edema and reduction of breast cancer infiltration, stabilization or reduction of the tumor size by the palpation examination, straightening and change in a positive direction of pathological form of the nipple, decrease of a pain syndrome. 2. Laboratory data:
The positive dynamics of laboratory parameters: X-rays - with stabilization or reduction of the tumor progression, improvement of laboratory dynamics during mammography.
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Criteria for evaluating the efficiency of the drug Flaraxin in the treatment of melanoma: 1. Clinical data:
The disappearance or reduction of the severity of subjective symptoms of antitumor process: improvement of general health, the appearance of appetite, normalization of mental and emotional status. The disappearance or reduction of the severity of objective indexes of antitumor process: reduction of edema and reduction of infiltrative lesion of skin surface, reduction of pain syndrome. 2. Laboratory data:
The positive dynamics of laboratory parameters: a histological study of tumors - stabilization or decrease in the progression of neoplastic process.
8.2. Criteria for the evaluation of patient general state in dynamics. Evaluation of the efficiency under experimental drug Flaraxin. Effectiveness of experimental drug was held by the researcher and the patient on the basis of above mentioned criteria in points on the following scale: 5 4 3 2 1 points - significant improvement; points - improvement; points - no changes; points - slight deterioration; point - significant deterioration.
Tolerability criteria of the drug Flaraxin. Tolerability of experimental drug was assessed on the basis of subjective symptoms and sensations reported by the patient, and objective data obtained by the researcher in the treatment process. The dynamics of laboratory parameters, as well as the frequency of occurrence and character of adverse reactions were investigated. Tolerance of drug was estimated by the researcher in points (scores) on the following scale: 4 Very good 3 Good 2 Satisfactory 1 Unsatisfactory 0 Very unsatisfactory Side reactions are absent, there is no deterioration of the laboratory parameters Observed minor side effects that does not cause serious problems to the patient and do not require discontinuation of the drug application Observed side effects that affect the patient's condition, but do not require discontinuation of the drug application Side reactions have a negative impact on the patient's condition and its require discontinuation of the drug application Side effects are danger to life or health, and require additional medical interventions
Statistical data processing was performed by parametric Fisher-Student method with the calculation criteria of validity. All Side effects encountered during the testing of the drug and marked by the patient or doctor were registered in the individual registration form and medical history.
9. Evaluation of the treatment efficiency. During clinical study was find out an increase in life expectancy of patients in experimental group in comparison with control group, and depending on the stage of the tumor, histological type of the tumor, the localization of metastases and the number of treatment courses. Findings are presented in tables.
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9.1. General characteristics of patients in groups. For the realization of clinical trial on drug FLARAXIN were selected two groups of patients within each diagnosis: With the diagnosis of lung cancer, aged from 31 till 70 years with stages III and IV stage of the tumor (experimental group - 50 people, 38 men and 12 women, and a control group - 20 people, 11 men and 9 women) in the experimental group on histological structure: the structure of squamous cell cancer was observed in 23 cases, in 18 cases adenocarcinoma, in 6 cases - small-cell carcinoma, 3 patients experienced carcinoma simplex; in the Control group: in 7 cases with structure of squamous cell carcinoma, 4 - adenocarcinoma, 3 - small-cell carcinoma in 6 patients had carcinoma simplex. With the diagnosis of breast (mammary gland) cancer, women aged from 31 till 70 years on II, III and IV stage of the tumor (experimental group - 40 people and a control group - 20 people) With the diagnosis of cervical cancer, women aged from 31 till 80 years with I, II, III and IV stage of the tumor (experimental group - 60 people and a control group - 25 people) in the experimental group on the histological structure: in 46 cases was squamous cell carcinoma in 11 - adenocarcinoma, 3 patients experienced clear-cell carcinoma, and in the control group on the histological structure: in 16 cases was squamous cell carcinoma, 4 - adenocarcinoma, in 5 patients had clear-cell carcinoma. With the diagnosis of melanoma, aged from 20 till 70 years with I, II, III and IV stage of the tumor (experimental group - 60 people, 46 women and 14 men, and a control group - 25 people, 13 women and 12 men). Patients of all experimental groups received experimental drug "FLARAXIN", produced by Scientific and Treatment Center for Cancer Curing "PHOENIX" Ltd (Kharkov, Ukraine), as follows: the drug was injected intravenously in doses of 1-2 mg/kg 1 time a day, during 16 days on a daily basis - I course of Flaraxin treatment, the interval between courses was 30 days, only maximum III courses was recommended during patients treatment, patients of the control group received the recommended standard therapy. 9.2. Evaluation of the direction flow for the Cancer process During the trial for all patients included in the study were conducted examination using clinical, laboratory and instrumental methods with the following parameters: physical examination (inspection, survey), the subjective evaluation of well-being of patients, radiological and histological examination of the tumor, the clinical blood analysis, clinical analysis of urine before start of the treatment and after end of the treatment course. Also in the examination were included special methods depending on the nosology of the tumor: lung cancer - bronchoscopy, cervical cancer - colposcopy, melanoma X-ray examination was not carried out. 9.3. Dynamics of the patients general condition indexes in experimental and control groups. Clinical observation and laboratory studies were conducted in dynamics - before treatment, after the end and at the beginning of the next course of treatment, at 17, 47, 65, 95, 113 days since the start of the study. During the study we found out a statistically significant increase in life expectancy of patients in the experimental group compared with the control group, depending on the stage of tumor, the distribution was as follows / Table 4/: Table 4. Comparison of resultant estimation of life expectancy in patients receiving the drug "FLARAXIN" (experimental group) and receiving standard therapy (control group), depending on the stage of the tumor. Stage of cancer I stage II stage III stage IV stage process Life duration, Exp Control Exp Control Exp Control Exp Control onths group group group group group group group group Lung cancer 9,70,5 6,40,8 3,60,4 5,10,3 Breast cancer 11,80,5 9,30,9 7,20,8 4,60,6 6,30,4 6,50,3 Cervical cancer 12,80,8 10,90,6 8,71,2 3,40,7 5,80,3 3,10,2 3,10,6 4,40,3 Melanoma 12,50,9 11,80,6 9,20,8 3,50,5 6,10,4 3,10,3 4,10,6 5,60,4 <0,05 in relation to the experimental group The data in table 4 shows (p <0,05) significant increase in life expectancy in groups of patients treated with the experimental drug FLARAXIN, especially in the early stages of the disease and compared with control groups of patients. Similar positive trends in increasing of life expectancy were found in the experimental groups: lung cancer and cervical cancer according to histological tumor type and compared with control groups of patients (Table 5).
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Table 5. Dependence of life expectancy in patients receiving the drug "FLARAXIN" (experimental group) and receiving standard therapy (control group), depending on the histologic type of tumor. Lung Cancer Small-cell * Undifferentiated * Squamous-cell * Glandular cancer cancer cancer cancer Exp Control Exp Control Exp Control Exp Control group group group group group group group group 5,30,1 1,10,1 6,20,3 3,10,3 7,80,3 4,00,2 9,20,4 3,80,3 Adenocarcinoma Clear-cell carcinoma Squamous-cell cancer Exp Control Exp Control Exp Control group group group group group group 5,40,3 3,10,3 7,60,6 4,60,4 8,21,1 3,60,4
Life duration, month Cervical cancer Life duration, month
<0,05 in relation to the source data The obtained data in Table 5 give a statistically significant rising of life duration (p <0,05) for patients who received the experimental drug FLARAXIN with glandular, squamous-cell, undifferentiated, small cell lung cancer and patients with clear-cell carcinoma, adenocarcinoma and squamous-cell Cervical Cancer in comparison with Control groups of patients. Also during the study were marked dependence of life duration and the results of treatment with metastases in experimental groups of patients with melanoma, lung cancer and breast (mammary gland) cancer (Table 6.1, 6.2, 6.3). Table 6.1. Dependence of life expectancy in patients receiving the drug "FLARAXIN" (experimental group) and receiving standard therapy (control group), depending on the localization of metastatic spreading process (Melanoma). Localization of metastases 1 Skin and soft tissue 2 Trema 3 Lymph nodes 4 Visceral organs 5 Bones 6 Brain 7 Multiple organs <0,05 in relation Quantity of patients 11 4 13 6 4 3 19 Subjective effect 10 (91%) 3 (75%) 9 (69%) 4 (100%) 2 (67%) 13 (68,4%) Without effect 1 (9,1%) 1 (25%) 4 (31%) 6 (100%) 1 (33%) 6 (31,6%) Stabilization of the process 3 (27,3%) 3 (31%) 2 (66,6%) 5 (26,3%) Partial regression 6 (54,6%) 3 (75%) 9 (69%) 1 (33%) 10 (52,6%) Complete regression 2 (18,2%) 1 (25%) 1 (7,7%) 1(5,3%) Life duration, month 8,01,9 6,06,8 4,02,7 2,50,3 2,80,2 5,80,2 4,10,4
to the source data
Statistically significant results (p <0,05) presented in Table 6.1 indicates that the application of the experimentaldrug FLARAXIN for patients diagnosed with melanoma, had a positive impact on significantly increasing life duration and improves general health (reduces pain, general weakness, dizziness, increasing work abilities) in patients with metastases in the skin and soft tissue, lymph nodes, vulva, and multiple organ metastasis in comparinson with metastasis to visceral organs, bones, as a result of drug treatment FLARAXIN has most positive influence for patients with metastases in skin and soft tissue, on the second place - metastases in lymph nodes, on third place were patients with multiple metastases, on a fourth place - metastases in vulva and has no influence on a patients with metastases in bones and metastases in the visceral organs. Table 6.2. Dependence of life expectancy in patients receiving the drug "FLARAXIN" (experimental group) and receiving standard therapy (control group), depending on the localization of metastatic spreading process (Lung cancer). Localization Quantity Subjective Without Stabilization Partial Complete Life of metastases of effect effect of the regression regression duration, patients process month 6,07,7 1 Pleura 10 2 (20%) 8(80%) 2 (20%) 6(60%) 5,04,7 2 Lymph nodes 17 13 (76,4%) 4(23,6%) 8 (58,8%) 4(23,5%) 2(11,8%) 3 Lungs 6 5 (83,3%) 1(16,7%) 3 (50%) 2(33,4%) 1(16,7%) 8,20,3 4 Bones 4 4(100%) 2,30,3 5 Liver 5 5(100%) 5 (100%) 2,10,2 6 Multiple 5 5(100%) 3 (60%) 5,00,1 organs 7 Brain 3 2(66,6%) 1(33,4%) 1(33,4%) 1(33,4%) 1(33,4%) 5,70,1 <0,05 in relation to the source data
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The results presented in Table 6.2 show that the application of experimental drug FLARAXIN for patients diagnosed with lung cancer, has a positive impact on increasing life duration and improves general health (reduces pain, general weakness, dizziness, increased working efficiency), in patients with metastases in pleura, lymph nodes, lungs, multiple organs and brain in comparison to patients with metastases in bones and liver (p <0,05). Positive results of the treatment with FLARAXIN were for patients with metastases: On the first place - in lymph nodes, on second place - pleura, on a third - in lungs and on fourth - metastases in brain and on fifth - in multiple organs, much worse were results for patients with metastases in the liver and in bones. Table 6.3. Dependence of life expectancy in patients receiving the drug "FLARAXIN" (experimental group) and receiving standard therapy (control group), depending on the localization of metastatic spreading process ((Mammary gland) Breast cancer). Localization Quantity Subjective Without Stabilization Partial Complete Life of of effect effect of the regression regression duration, metastases patients process month 2,131 1 Lymph nodes 8 7(87,5%) 1(12,5%) 4(50%) 4(50%) 8,02,01 2 Lungs 4 2(50%) 2(50%) 1(25%) 2(50%) 1(25%) 3 Bones 2 2(100%) 2(100%) 7,20,5 4 Pleura 2 2(100%) 2(100%) 8,10,4 5 Liver 2 2(100%) 5,60,5 5 Skin 2 2(100%) 2(100%) 4,60,3 6 Multiple 17 13(76,4%) 4(23,6%) 8(47%) 6(35,3%) 6,20,4 organs <0,05 in relation to the source data The obtained data in Table 6.3 indicate that the application of experimental drug FLARAXIN for patients diagnosed with breast cancer (p <0.05) significantly have positive impact on increasing of life duration and improve general health (reduces pain, general weakness, dizziness, increases working efficiency), for patients with metastases in lymph nodes and in lungs, in multiple organs, in pleura, skin metastases in comparison to metastasis: in the liver and bones. Positive results of the treatment with FLARAXIN were for patients with metastases: On the first place - lymph nodes, on second place - lungs, on a third - multiple organs and on fourth - metastases in pleura, then with skin metastases. Much worse situation were for patients with metastases in bones and liver. It was also revealed a positive trend in life duration depending on the number of Flaraxin courses applied in the experimental groups of patients (Table 7). Table 7. The total evaluation of life duration for patients receiving the drug "FLARAXIN" (experimental group) dependent on the number of Flaraxin treatment courses. Quantity of treatment courses Quantity of patients Average Life duration, months Melanoma 5,0 9,3 I treatment course 23 (38,3%) 7,0 2,6 II treatment courses 10 (16,7%) 1,1 4,01 III treatment courses 27 (45%) Lung cancer 3,0 4,2 I treatment course 29 (58%) 6,0 6,6 II treatment courses 15 (30%) 8,0 9,8 III treatment courses 6 (12%) Cervical cancer 2,0 6,2 I treatment course 26 (43,3%) 3,0 6,3 II treatment courses 11 (18,3%) 6,0 7,7 III treatment courses 23 (38,4%) (Mammary gland) Breast cancer 4,0 2,5 I treatment course 11 (27,5%) 9,0 4,9 II treatment courses 12 (30%) 4,1 4,71 III treatment courses 17 (42,5%) <0,05 in relation to the source data Thus, life duration in the experimental groups of patients in all nosological forms of cancer have significant improvement (p <0,05) and were directly proportional to the number of Flaraxin treatment courses. During clinical trial for all patients included in the research were carried out the clinical blood analysis (hemoglobin, erythrocytes, leukocytes, platelets, leukocyte counts, color index, ESR) and clinical analysis of urine (amount, pH, specific gravity, leukocytes, erythrocytes, cylinders, epithelial cells, salts, mucus) before treatment and after completion of the course. During this process no abnormalities in blood and urine in the experimental groups before, during and after treatment were identified, all indicators of laboratory analysis also were in norm.
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10. Evaluation of the experimental drug Flaraxin on tolerability, on allergic and local irritating action, on general and side (toxic) reactions. Only two cases with side effects were registered during all process of clinical trial were reported on patients with cervical cancer diagnosis and on 1 patient with melanoma. Side reactions were observed in the form of nausea and vomiting after injection of experimental drug FLARAXIN and this reaction was possible related with previously carried out chemotherapeutic treatment. Later, after 3-4 days of FLARAXIN treatment, all allergic reactions disappeared in these patients. Such cases were exceptional and were not considered as side effects due to low intensity, but, nevertheless, have been identified as satisfactory tolerability of experimental drug. In a group of patients with breast cancer was one patient had allergic reaction in the form of urticaria, which was cupped by standard anti-allergic therapy, and was evaluated as individual intolerance to the iodine containing drugs. Based on subjective data and objective results of clinical and laboratory studies of patients in the treatment cancer process by experimental drug "FLARAXIN" were found that the tolerability of the experimental drug was "Good", except cases with individual intolerance to drug. The laboratory data on patients conditions during treatment are testifying that no significant difference were observed in the investigated indices before and after treatment, which indicates that drug FLARAXIN does not have general toxicity and sensitizing effect on the patients. 11. Discussion of the results and main conclusions. Clinical trial of therapeutic effectiveness and endurability of the drug FLARAXIN showed: 1. Drug FLARAXIN produced by Scientific and Treatment Center for Cancer Curing PHOENIX (Kharkov, Ukraine) has a high anti-tumoral activity and good endurability, which gives the ground to recommend FLARAXIN for wide clinical application in practice of oncologic diseases treatment, especially on primary stages of tumoral process and in combination with traditional methods of treatment as a carcinostatic drug. 2. Drug FLARAXIN also should be recommended between the courses of the traditional treatment (chemotherapy and radio-therapy) and after the end of the treatment, as a remedy of adjuvant and non-adjuvant therapy, because it can prevent relapse of the cancer and metastasis (Mts) spreading of oncologic process in the body of patient. 3. In the case of obtaining objective effect (tumor regression or stabilization) the treatment should have prolongation until the positive effect will remain. 4. Drug FLARAXIN has a good endurability and does not have allergic reactions, besides the cases of individual intolerance to iodine containing drugs.
Executors: Chief of the III Oncological Department (mammary gland cancer) of CSMU d.m.s, professor A.G.Filenko Chief of the Radiological Department (cervical cancer) of CSMU d.m.s., professor N.I.Verizhnikova Chief of the II Oncological Department (melanoblastoma) of CSMU d.m.s., professor I.V.Pohvalin Rector of the Crimea State Medical University (CSMU) named after S. I. Georgievsky MD, professor - A.A.Babanin Leader: Chairman of the Oncology Department of the Crimea State Medical University (CSMU) named after S. I. Georgievsky MD, professor V.M.Efetov Responsible Executor: Assistant of the Oncology Department (lungs cancer) of CSMU named after S.I.Georgievsky d.m.s, professor A.V.Protsenko
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EXTRACT 3
From the report on clinical trial (3d PHASE) of a therapeutic effectiveness and endurability of the preparation FLARAXIN Oncology Department of Crimea Medical University named after S.I.Georgievsky
CONCLUSIONS Clinical trial of therapeutic effectiveness and endurability of the preparation FLARAXIN showed: 1. FLARAXIN produced by Scientific and Treatment Center for Cancer Curing PHOENIX (Kharkov) has a high antitumoral activity and good endurability, which gives the ground to recommend FLARAXIN for wide clinical application in practice of oncologic diseases treatment, especially on primary stages of tumoral process, in combination with traditional methods of treatment as a cancerostatic preparation. FLARAXIN also should be recommended between the courses of the traditional treatment (chemotherapy and radio-therapy) and after the end of the treatment, as a remedy of adjuvant and non-adjuvant therapy, because it can prevent relapse of the cancer and metastasis (Mts) spreading of oncologic process in the body. In the case of obtaining objective effect (tumor regression or stabilization) the treatment should have prolongation until the positive effect will remain. FLARAXIN has a good endurability and does not have allergic reactions, besides the cases of individual intolerance to iodine containing medications.
2.
3. 4.
Scientific leader of the theme: Chairman of the Oncology Department of Crimea Medical University named after S.I.Georgievsky Chief executor: Assistant of the Oncology Department of Crimea Medical University named after S.I.Georgievsky Executors: Chief of the III Oncology Department of Crimean republic clinical oncologic dispensary (cancer of the mammary gland) Chief of the Radiological Department of Crimean republic clinical oncologic dispensary (cancer of the neck of the womb) Surgeon-oncologist II Oncology Department of Crimean republic clinical oncologic dispensary (melanoblastoma)
Prof. DMS, V.M.Efetov
Dr. A.V.Protsenko
Dr. A.G.Filenko
Dr. N.I.Verizhnikova
Dr. I.V.Pochvalin
Simferopol 2001
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REPORT ON THE TRIAL OF INTERFERONOGENIC ACTIVITY OF ANTITUMORAL PREPARATION FLARAXIN
Prof. DMS. N.Ya.Spivack D. K. Zabolotny Institute of Microbiology and Virology of NAS of Ukraine (Department of interferon and immunomodulators problems) Interferonogenic activity of FLARAXIN was studied in experiments in vitro on white mongrel mice (male, body weight 18-20 g). The preparation was diluted on 5% glucose solution. 0,2 ml of it were injected intra-abdominally in concentration 5,50 and 250 g/mouse. The well-known inductor interferon Poly I:C /Sigma/ was used as a control, as well as 5% glucose solution or physiological solution (placebo). In 6, 24, 48 and 72 hours the mice were decapitated and blood plasma was received, in which the level of interferon was tested. Besides the factor of tumor necrosis was defined. The presence of interferon was defined on Cito-Pathogenic Action (CPA) of test-virus suppression (virus of vesicular stomatitis of Indiana strain in doze 100 CPA50/in the culture of inoculated cells L-929 or Anti Tuberculosis Preparations (ATP), grown in 96-hole cultural panels (Linbro). The size reverse to probe dilution under which 50% cells defense from cyto-pathogenic action (CPA) of test-virus is observed was taken for the titer of interferon. The factor activity of tumor necrosis in plasma was defined according to cytolithic action on target cells L-929, influenced by actinomycin-D (Serva), using spectro-photometric test with crystal violet (Methodical recommendations, Kiev, 1994). RESULTS Results of interferon levels definition are presented in Table 1. Table 1. Presence of the similar to the interferon activity in the mices blood plasma after flaraxin injection. Time after injection of the medicine [hours] 6 24 48 72 5 40 40 40 50 320 320 160 250 80 80 40 50 <4 <4 <4 50 <4 <4 <4 50 <4 <4 <4
FLARAXIN Poly I:C 5% glucose physiological/salt solution As it follows from Table
1, FLARAXIN has interferogenic activity. As the doze of 5g/mouse has already had the ability to stimulate the formation of interferon. However the most optimum doze is 50 g/mouse. Using this doze the level of interferon in animal organism is higher and remains the same during a long period of time (up to 72 hours). At the same time all known inductors of interferon including Poly I:C have short time activity under interferon induction. That is why FLARAXIN property to support interferon production for a long time makes it quite interesting and perspective for application under treatment and prophylactics of pre-tumoral, tumoral processes, as well as virus infections of CNS and the so called slow virus infections, to which AIDS, Dispersed Sclerosis and others. In other series of experiments in 24 and 72 hours after injection to animals optimal doze of the preparation (50g/mouse), the animals were extracted spleen, the suspension of splentocites was prepared and functional abilities of immunocomponent cells were studied, as well as the type of inducted interferon was defined ( alpha or -gamma). For this purpose inductors of interferon Virus of Newcastle Disease (VND) and phytohemagglutinin (PHA) were added to the suspension of splentocites. The splentocites of intact animals served as control. The results of these experiments are presented in Table 2.
Titre of interferon [a.u./ml]
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Table 2. Interferon production by the mice splenocites after previously injected FLARAXIN.
Titre of interferon [a.u./ml]
Inductor of interferon VND exp 1 VND exp 2 PHA exp 1 PHA exp 2
splenocytes of the intact animals /24h/ 640 320 80 80
Mice splenocytes after FLARAXIN injection /24h/ 640 640 160 160
Splenocytes of the intact animals /72h/ 320 320 40 80
Mice splenocytes after FLARAXIN injection /72h/ 640 640 160 320
The received data testify for some growth of splentocites ability of animals, which previously were injected the preparation, to synthesize interferon in vitro under influence of interferonogen. As it follows from table 2, during application of VND as an inductor, i.e. under induction of -interferon, the synthesis growth twice (if the preparation was injected before 72 hours of the extraction of spleen in mice). During application of interferon PHA as an inductor (induction of -interferon) the essential strengthening in interferon production takes place in 4 times. These data can be used for processing of optimal scheme of preparation injection for treatment. Besides the presence of tumoral necrosis factor in animals plasma after injection FLARAXIN to them was studied. In this case it was stated, that only the use of high dozes of preparation (250 g/mouse) lead to essential growth of Tumor Necrosis Factor (TNF) level in comparison with control. As for the type of induced interferon it became thermolable, which is a characteristic feature for -gamma-interferon, but for the final statement it is necessary to carry out additional experiments on acid-lability and antigen characteristic feature. Thus, on the basis of the carried out experiments it was stated, that the preparation FLARAXIN has interferonogenic activity, as well as inducts in organism the formation of tumor necrosis factor (TNF). It is necessary to conduct additional research on definition of optimal schemes of preparation injection, taking into account hypo-reaction of the organism on frequent injections of interferon inductors.
Chief of the Department of Interferon and immunomodulators problems of D. K. Zabolotny Institute of Microbiology and Virology of NAS of Ukraine
Prof. DMS. N.Ya.Spivack
37
EXTRACT FROM THE REPORT ON THE TRIAL OF IMMUNOMODULATING CHARACTERISTICS OF THE PREPARATION FLARAXIN
Prof. DMS. V.G.Bordonos O.O. Bogomolets National Medical University of NAS of Ukraine (Department of experimental and clinical immunology)
CONCLUSIONS
1.
Under the effect of the FLARAXIN action the massive destruction of tumor tissue occurs with further resorption of decay products by the reticuloendothelial system of organism. As a result the binding of these products, which have protein structure and carriers antigenic information, the formation of the corresponding antibodies occurs which form an additional quantity of complexes antigen-antibody (Circulating immune complexes - CIC). Conducting the course of FLARAXIN treatment led to a substantial increase in the activity both of the antibodydependent and natural killer activity of lymphocytes. The conducted research of the FLARAXIN influence on the indices of various parts of immune system in patients with oncologic pathology testifies that systemic immunodeficiency caused by tumoral process is subjected to positive correction. The recovery of leading mechanisms of immune processes with the help of Flaraxin is accompanied by improvement of general clinical state of patients, leads to reduction, and in some cases to full exclusion of metastatic spreading process, diminution of neoplasm size.
2.
3.
Chief of the Department of Experimental and clinical immunology of O.O. Bogomolets National Medical University of NAS of Ukraine
Prof. DMS V.G.Bordonos
38
PATHOPHYSIOLOGICAL MECHANIZMS OF ANTIPROLIFERATIVE FLARAXIN EFFECT REALIZATION
Executor: Professor, Dr. A.V.Artemov Filatov Institute of eye diseases and tissue therapy AMS of Ukraine (Oncology Department) Flaraxin is an anti-tumoral remedy of vegetable origin, one of the remedies with high cancerolitic effect under absence of toxicity (LD50 for mices in the range of 115-350 mg/kg of the mass body). The studies that was done in the leading scientific institutes of the National Academy of Science of Ukraine shows Flaraxin has antioxidant properties, stimulates production of endogenic interferon and tumor necrosis factor (TNF). Besides clinical application of flaraxin experience, namely the cases when the remedy gives complete clinical remission of tumoral process, accompanied by tumoral ganglions resolving, allow doubting, that similar effect is stipulated by only mentioned above remedy properties. Its absolutely logical to suppose, that flaraxin is able to have a direct cytotoxic effect on tumoral cells, as it is demonstrated for the non-toxic anti-tumoral medicine Ukrain. Main interest represented by Flaraxin selective cytopatic action phenomenon only on tumoral cells, besides this Flaraxin affects on non-malignant tumors in contrast to cytostatics medications. For elucidation of this universal mechanism of anti-proliferative action of Flaraxin we addressed to recently stated phenomenon of selective connection of cytostatics with serumal (whey) proteins in oncological patients. On the basis of this phenomenon the diagnostic test was designed, tested and patented. However, to our mind, the phenomenon of selective connection of anti-tumoral preparations with oncoassociated proteins opens new perspectives in the study of the mechanism of their action on tumoral process. Materials and methods. The trial was carried out on 40 patients with various forms and stages of malignant oncological process, as well as 10 patients with non-tumoral pathology and non-malignant tumors. The object of the trial was blood serum of the patients in which the content o SH-groups was defined before and after the contact with anti-tumoral preparations. Thus, the received serum was separated on several parts in accordance with the preparations used for testing. After incubation during 2 hours under t 37C in relation 10:1 (serum: preparation) by amperometric titration the number of free non-protein mkm/l was defined. In the control probe the serum was without addition of preparations. The following preparations: VINBLASTIN (the firm Hedeon Richter), CYCLOPHOSFAN (AS Biochemist), UKRAIN (Vena Novitskapharm) and FLARAXIN (STCCC Phoenix, Kharkov) were used as reagents. The research was fulfilled on the basis of immunology laboratory 411 of the Main Hospital of the Southern Operational Command (Odessa). Results and their discussion. Most of the investigated cancer patients had partly high level of non-protein SH-groups in blood serum: 17,17,4 mkm/l. This is stipulated by the fact that most of the patients were with heavy stages of tumoral process, accompanied by violations of hemorheological homeostasis. Presence of free non-protein SH-groups in this situation reflects conformational non-stability of serum proteins on the background of catabolic processes predominance. In connection with level of nonprotein SH-groups in native serum, absolute indicators of selective binding for VINBLASTIN and CYCLOPHOSFAN were higher, then in the earlier conducted research (table. 1). Table. 1. Concentration of non-protein SH-groups in reaction mixtures of examined oncopatients (BS blood serum) BS BS BS BS + + + + Reaction mixture Vinblastin Cyclophosfan Ukrain Flaraxin mixture Level of non-protein SH-groups mkm/l Mm 18,4 8,3 20,7 7,1 23,6 5,7 32,2 9,9
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From the table 1. is seen, that Flaraxin gives the highest indices of selective binding with proteins of blood serum in patients. The interpretation of this phenomenon, to our mind, is directly connected with the analysis of pathophisiological mechanisms of anti-tumoral activity of the Flaraxin. The same we can say about another non-toxic medication Ukrain Mentioned above related with patients that have malignant forms of tumoral process. During examination of blood serum of patients with non-malignant tumors was found unexpected picture. Blood serum of patients with fibrocystic mastopathy (4 cases), uterus fibromyoma (2 cases), prostate adenoma (1 case), and thyroid ganglion adenoma (1 case) was examined by us. In all cases VINBLASTIN and CYCLOPHOSFAN did not give the selective binding with proteins of blood serum, FLARAXIN gave selective binding in 7 from 8 cases, UKRAIN in 6 cases. Medium indices for FLARAXIN comprised: 8,5 3,2 mkm/l. The ability of FLARAXIN to connect with proteins of blood serum of the patients with non-malignant tumors was exposed by us, i.e. the ability to give denaturizing injures of these proteins and it is correlated with the propositions mentioned above, that anti-tumoral effect of Flaraxin is realized through this mechanism of bindings with oncoassociated proteins and that gives denaturizing injures to this proteins. As it is known, cytostatics do not act on non-malignant tumors, they also do not give denaturizing injures (speaking about only injures, realized through tyolodysulfide bounds) of the proteins, taking place under non-malignant tumoral processes. At last, in the casual examination of blood serum in pregnant (2 cases) we found quite high selective connection in relation to FLARAXIN Mm = 25,6 0,4 mkm/l. Neither cytostatics nor UKRAIN in these cases did not show any selective connection. Only Flaraxin was able to give this selective connection with blood serum proteins. Thus, we have all reason to consider, that FLARAXIN realizes its anti-prolyferative effect through denaturizing injures of onco-fetal proteins. These injures are realized by conformational vulnerability (labilisation) of tyolodysulfide bounds in this group of proteins. Probably such conformational vulnerability of oncoassociated proteins of embryonic period is doe to execution exclusively prolyferative function by them, requires a different level of tertiary organization of protein. Main conclusions. 1. 2. 3. FLARAXIN in comparison with cytostatics, has the ability to give denaturizing injures to oncoassociated proteins, realized through labilized tyolodysulfide bounds. In contrast to the cytostatic medicines FLARAXIN shows denaturizing effect of mentioned above type on proteins of blood serum in patients with non-malignant tumors and pregnant. Anti-tumoral effect of FLARAXIN is stipulated by its universal antyprolyferative properties, realized through mechanism of denaturizing injure of labialized tyolodysulfide bounds of proteins that participate in proliferative process.
Chief of the Oncology Department of Filatov Institute of eye diseases and tissue therapy AMS of Ukraine
Prof., Dr. A.V.Artemov
40
EXECUTION OF THE TEST ON SELECTIVE CONNECTION
Professor, Dr. A.V.Artemov Filatov Institute of eye diseases and tissue therapy AMS of Ukraine (Oncology Department)
1. 2. 3. 4. 5. 6.
Taking not less than 10 ml of blood from vein. Obtaining serum, dividing it into equal parts by the number of tested drugs, one part - control. Into all parts, except control, reagent should be added in concentration 10:1. The reagent solution is necessary to select empirically. Mixture of serum with reagent is incubated during 2 hours under temperature equal 37C. After incubation should be done deproteinization of serum. In deproteinized serum free non-protein SH-groups should be defined.
For spectrophotometric definition of SH-groups it is necessary to select the level of reagents solution (cytostatics, flaraxin or others).
Selection of preparations solution.
1. 2.
First therapeutic solution should be taken. Then definition of non-protein SH-groups of healthy donors in control probe and after addition of the preparation with aim to compare later. Correctly selected solution must not cause addition of SH-groups in comparison with control. If it is not happend, then therapeutic solution must be done during longer period of time.
41
ESTIMATION OF ANTIOXIDANT ACTIVITY OF FLARAXIN ON STARTING STAGES OF FREE-RADICAL OXIDATION
(experimental trial)
Executor: Professor, Dr. A.V.Artemov Filatov Institute of eye diseases and tissue therapy AMS of Ukraine (Oncology Department)
One of the mechanisms of antioxidant activity of Flaraxin, as our previous report showed, is influence of Flaraxin on tyoldysulfide bounds of proteins. After Flaraxin application the changes of protein redox-potential is taking place and this process accompanied by conformational proteins changes, and in particular, connected with processes of immunogenesis and oncogenesis. The result of these changes, as clinical trial demonstrated, is the growth of cytostatic activity of immune system cells and apoptosis of tumoral cells activation. Besides it is well-known, that bioflavonoids have antioxidant properties. However antioxidant activity of Flaraxin was not specially studied. Mechanism of free-radical oxidation and connected with it antioxidant system are considered as the most important chain of many pathology processes. Structural-functional integrity of cells and organism tissues essentially depends on freeradical oxidation mechanism, which is directly connected with the senescence processes and tumoral transformation. Free-radical oxidation caused by active forms of reactive oxygen, which are formed as a result of fermentative activity of oxidoreductase. In this case oxygen ions (O2) and hydrogen peroxide (H2O2) are formed. Definite role in this process belongs to auto-oxidation of catecholamines. Mechanism of injuring action (damage) is realized through oxygen ions and hydrogen peroxide interaction with the formation of hydroxyl radicals (R-O-H) and free oxygen (O2 ). This leads to inactivation of various proteins, destructive changes of polysaccharides and mutagenesis stimulation due to DNA damage. Active forms of oxygen initiate peroxide oxidation of fat acids and their derivatives that leads to carbonyl compounds, bounding with nucleic acids and proteins. Obviously, antioxidant defense can become an important factor on the way of mutagenic changes, leading to neoplastic cells and tumoral progression. Lately with the aim of influence on free-radical oxidation antioxidants are used in treatment of ischemic diseases of various localization. Such substances with antioxidant activity, as alpha-tocoferol, dybunol, oxypyridines are widely used today. However many famous antioxidants have serious deficiencies; they act only on final stage of free-radical oxidation, and during destruction of free radicals of poly-non-saturated fat acids they form toxic products ( ). Clinical approbation of Flaraxin demonstrated presence of anti-tumoral, antivirus and immunomodulating properties ( ). Estimation of antioxidant activity of the Flaraxin is of great interest, considering that free-radical oxidation plays an important role in oncogenesis. It should also be mentioned, that the study of free-radical injuries (damage) as well as estimation of antioxidant defense in the process of chemo-therapeutic treatment of oncology patients has already attracted attention of oncologists ( ). We consider that antioxidants role is important also for prophylactics of early and late relapses, i.e. as remedies of adjuvant and non-adjuvant therapy accompaniment. In this work we used the improved method of antioxidant activity estimation of antioxidants on the starting stages of free-radical oxidation on inhibition of superoxide-radical in reaction of adrenaline auto-oxidation into adrenochrome in alkaline medium.
42
Materials and methods. Into 10 ml flask of spectrophotometer SF-26 was added 2.0ml of 0,15M natrium-carbonate buffer with the addition of 3x10-4ml ethylen-ediamine-tetra-acetic acid (EDTA) (pH 10,2) were inserted, then the solutions of the preparations under study were added. The reaction started with the addition of 0,4ml 2,25x10-3 M water solution of adrenalin. Original crystalline adrenalin was solved in distilled water and by addition of chloral-hydrogen acid the pH=2,25 was achieved. At first the index of extinction (E1) was defined, which reflected the speed of inhibition of adrenalin auto-oxidation, and then the index of extinction (E2) that reflects the speed of adrenalin auto-oxidation in presence of investigated preparations. The reaction was carried out under the temperature of 35-36C in spectrophotometer SF-26 under wave length =480nm, extinction time = 33min. Antioxidant activity of the preparations were expressed in percentages of inhibition of adrenalin auto-oxidation and calculated according by the formula:
E1 E1
Results and discussion.
E2
x100
In this work the preparation Flaraxin was used for the estimation of antioxidant activity on inhibition of superoxideradicale in the reaction of adrenalin auto-oxidation into adrenochrome. For the comparison of preparations the well-known preparation of antioxidant activity alpha tocopherol was taken as well as dymetilsulfoxide, which is one of the strongest reactivations of superoxidedysmutase, and also two chelate compounds of mercury: with cysteine (Mercurid-C) and with metionin (Mercurid-M). The results of the trial are presented in Table 1. Table1. Comparative antioxidant activity of Flaraxin and some other antioxidants (M+m; n=10) Preparation name Flaraxin Mercurid-C Mercurid-M alpha-tocoferol Dymetilsulfoxide Control Concentration mkMol/ml Optical density =480 nm 0,018+0,01 0,07+0,001 0,07+0,001 0,18+0,001 0,07+0,001 0,19+0,02 Antioxidant activity, % 85,7 8,8 7,8 5,3 43,9 -
2,5 2,5 -
Distinction is reliable in comparison with control, p0,001

Analysis of the data presented in this trial allow to speak about significant antioxidant activity of Flaraxin. By the way this activity is much higher, than in well-known antioxidant alpha-tocoferol and reactivator of superoxidedysmutase of dymetilsulphoxide.
Literature 1. 2. 3. L.V.Boytsova, Changes of the antioxidant system of glutathione as an index of cytotoxic effect of platidiama // V.V.Dunaev, I.F.Belenichev S.I.Kovalenko and others, Antiradical and antioxidant activity of derivatives of 1,2,4triazole and quinazolin with cerebral ischemia / / Ukrainian biochemical journal, 1996, t.68, 1. - P.100-103. V.G.Zaitsev, V.I.Zakrevskiy, The cells protection against exogenous and endogenous reactive oxygen species. Methodical approaches to the investigation. // Fundamental and applied aspects of modern biochemistry. Reports of the scientific conference devoted to 100 years anniversary of the Biochemistry Department of I.P.Pavlov National Medical University. , St.Petersburg, October 15-17, 1998,Volume 2,P.401-405. N.A.Korovina, I.N.Zaharova, E.G.Obynochnaya, The application of antioxidants in pediatric practice. // Consilium medicine, 2003. n.5. - 9.
4.
43
CLINICO-MORPHOLOGICAL CHARACTERISTICS OF TUMORS AFTER FLARAXIN ACTION
Executors: Dr. A.I.Tkachenko, Dr. V.P.Shetilov, Dr. E.I.Oleynick Scientific and Treatment Center for Cancer Curing Phoenix
Generalized results of patients treatment with the application of anti-tumoral preparation FLARAXIN in STCCC PHENIX are presented in the tables. Groups of patients with some oncologic diseases of stomach, breast, lungs and intestine were studied. The results of patients treatment having some courses of FLARAXIN are presented in Table 1. From 24 patients only one had the course of treatment initially having the diagnosis of the III-rd stage, the rest of the patients had the course of treatment having the IV-th stage of the disease. Table 1. Results of patients treatment with stomach cancer under application of 1-3 courses of FLARAXIN and more.
Treatment results (stomach cancer) Stage of tumoral proc- After the 1-st course After the 2-nd course After ess develop- ImproveImproveNo No changes In In genment ment ment changes general eral Number Abs. % Abs. % Abs. % Abs. % In general 18 75 6 25 14 10 71 4 29 14 including 24 III stage. 1 100 1 1 100 1 patient IV stage. 17 74 6 26 13 9 69,2 4 30,8 14 23 patients 3 and more courses ImproveNo ment changes Abs. % Abs. % 12 12 86 85,5 2 2 14 14,3
According to these results it is clear, that the earlier the treatment is started, the higher the probability in final success. The patients in whom improvement began after the 1-st course had further improvement of their state. If after the 1st course improvement was shown in 74% with one recovery, after 3 courses improvement comprised 85,5%. The results of patients with breast disease treatment are presented in Table 2. Table 2. Results of patients with breast cancer treatment under application of 1-3 courses of FLARAXIN and more. Treatment results (breast cancer) Stage of tuAfter the 1-st course After the 2-nd course After 3 moral process No development Improve- No changes In gen- ImproveIn genment ment changes eral eral Number Abs. % Abs. % Abs. % Abs. % In general in36 68 17 32 44 33 75 11 25 34 cluding 54 III stage. 4 100 1 1 100 1 4 patients IV stage. 32 65,3 17 34,7 43 32 74,4 11 25,6 33 49 patients and more courses ImproveNo ment changes Abs. % Abs. % 26 1 25 76 100 75,8 8 8 24 24,2
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It can be said that on the III-rd stage the problem of the given disease can be solved without additional intrusion. On the IV-th stage only 65,3% of intrusion after the 1-st course in 65,7% of patients, after the 2-nd - in 74%, after the 3-rd in 75,8%.
The results of patients with lungs disease treatment are presented in Table 3. Table 3. Results of patients with lungs cancer treatment under application of 1-3 courses of FLARAXIN and more. Treatment results (lungs cancer) Stage of tumoral After the 1-st After the 2-nd course After 3 and more courses process develcourse opment ImproveNo ImproveNo ImproveNo In genIn genment changes ment changes ment changes eral eral Number Abs. % Abs. % Abs. % Abs. % Abs. % Abs. % In general in31 65 17 35 39 30 77 9 23 19 15 79 4 21 cluding 48 III stage. 1 50 1 50 1 1 100 2 patients IV stage. 30 65,2 16 34,8 38 30 78,9 8 21 19 15 79 4 21 46 patients
The results of patients with intestine disease treatment are presented in Table 4.
Table 4. Results of patients with intestine cancer under application of 1-3 courses of FLARAXIN and more. Treatment results (intestine cancer) Stage of tumoral After the 1-st After the 2-nd course After 3 process develcourse opment ImproveNo ImproveNo In genIn genment changes ment changes eral eral Number Abs. % Abs. % Abs. % Abs. % In general in24 62 15 38 21 17 81 4 19 19 cluding 39 III stage. 2 100 1 1 100 2 patients IV stage. 22 59,5 15 40,5 20 16 80 4 20 19 37 patients CONCLUSIONS 1. Analysis of the presented data are testifying high anti-tumoral activity of Flaraxin, especially on early stages of oncologic process development. The effectiveness of the Flaraxin under application on III-rd and IV-th stages become apparent in essential improvement of life quality in the majority of patients and rise of life duration which is approved by numerous clinical trials.
and more courses ImproveNo ment changes Abs. % Abs. % 16 16 84 84,2 3 3 16 15,8
2.
45
LIST OF PATIENTS
WHO RECEIVED COMPLEX TREATMENT WITH THE USE OF METHODS OF STCCC PHOENIX FROM 1997 TO 2008, EXCEEDING THE RESULTS OF CLINICAL TRIAL.
Patient Gvi-yan Ekaterina Yakovlevna, 1926 year of birth Diagnosis: Cancer of the left kidney T3NxMx. Treatment: She was operated and passed Poly-Chemotherapy. Tumor was growing. From 27/05/2002 till 12/07/2003 She received 4 Flaraxin courses. She feels good. All analyses did not show any pathology on 03.06.2005. (data on 2005). Patient Ya-ko Vladimir Alexandrovich, 1977 year of birth Diagnosis: Neuroblastoma (traumatic) cervical spinal cord dysfunctions. TxNoMo. Treatment: He was operated than relapse. From 11.02.2002 to 12.09.2004 He received 5 Flaraxin courses. On 07.06.2008 feels good. Right now married and has two children (data on 2008). Patient Sh-na Lidia Timofeevna, 1946 year of birth Diagnosis: Cancer of the right breast. T3N2Mo. Treatment: She was operated and passed Poly-Chemotherapy. Cancer process was progressing. From 03.04.2002 till 26.03.2003 She received 4 Flaraxin courses. On 26.03.2007 feels good without any metastasis and without relapse. (data on 2007). Patient Ry-va Vera Nicolaevna, 1930 year of birth Diagnosis: Cancer of the right breast. T4N1M1. Treatment: She was not operable and refuses to pass traditional PolyChemotherapy and Radiotherapy. From 20.11.2002 till 17.12.2003 She received 4 Flaraxin courses. On 20.08.2007 she feels good, working at home. (data on 2007). Patient Ba-ch Fenya Lukianovna, 1929 year of birth Diagnosis: Cancer of the left ovary. T3NxM1. Treatment: She was operated and passed chemotherapy. Cancer process was progressing. From 22.01.2002 till 10.02.2003 She received 4 Flaraxin courses. On 10.01.2006 she feels good (data on 2006). Patient Ko-tuk Vladimir Filimonovich, 1932 year of birth Diagnosis: Cancer of the larynx. T1NxMo. Treatment: He was operated and than passed radiotherapy. Cancer process was progressing. From 13.02.2002 till 10.10.2002 He received 3 Flaraxin courses. On 10.01.2006 He feels normal. No relapse and no metastasis were found (data on 2006). Patient Dr-va Ludmila Matveevna, 1931 year of birth Diagnosis: Cancer of the right breast. T4N1Mx. Treatment: She passed surgery, chemotherapy and radiotherapy. Cancer process was progressing. From 26.03.2002 till 01.02.2003 She received 4 Flaraxin courses. Her subjective state was stable. On 2.02.2006 Her common conditions is satisfactory (data on 2006). Patient Ta-ko Nina Fedorovna, 1949 year of birth Diagnosis: Cancer of the stump of the cervix T2NoMx. Treatment: She passed surgery, chemotherapy and radiotherapy. Cancer process was progressing. From 30.05.2002 till 05.12.2002 She received 3 Flaraxin courses. Her subjective state was stable. Her life quality is better on 10.02.2006 (data on 2006). Patient Ko-ya Kamila Michailovna, 1934 year of birth Diagnosis: Cancer of ovaries T3N1M1. Treatment: She passed chemotherapy and radiotherapy. Cancer process was progressing. From 16.06.2002 till 17.03.2003 She received 3 Flaraxin courses. Her state on 20.05.2003 was good. She moved to the Moscow (data on 2005).
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Patient D-ny Vladislav Vladimirovich, 1951 year of birth Diagnosis: Cancer of left kidney T4N1Mx. Mts in the para-aortal lymph nodes. Treatment: He did nephrectomy operation on 23.03.2000. After surgery He received 3 Flaraxin courses. On 25.02.2003 his conditions was satisfied. Patient M-v Alexander Naumovich, 1951 year of birth Diagnosis: Prostate cancer T4NxMo. Treatment: The traditional treatment was rejected because of spreading cancer process. From 17.05.2003 He received 3 Flaraxin courses and detoxication therapy. For the moment he feels satisfied on 14.03.2008 (data on 2008). Patient M-ko Ivan Michailovich, 1926 year of birth Diagnosis: prostates gangliome cancer, metastasis into lower sacral spine. Pathological and Histological Conclusion (PHC) adenocarcinoma. Treatment: He received palliative radiotherapy and incomplete course of chemotherapy due to cardiac arrhythmias it was not possible to continue appointed treatment. The patient received 3 Flaraxin courses. His condition stabilized (data on 1999). Patient K-r Vasiliy Pavlovich, 1935 year of birth Diagnosis: prostate adenoma. Suffers from 1997. He refused surgery because of heart attack. Treatment: He received 18.09.1997 3 Flaraxin courses. He feels good. Urination is free (Data on 2001). Patient B-er Grigory Grigoryevich, 1920 year of birth Diagnosis: prostate adenoma. Treated from 21.10.1997. He received 3 Flaraxin courses. Urination was restored, no pain anymore in the lumbar region. He is working (Data on 1999). Patient V-ko Leonid Savelyevich, 1934 year of birth Diagnosis: prostate cancer, last IV-stage, ascites, chronic bronchitis. PHC small asinar adenocarcinoma. Treatment: He received 3 Flaraxin courses. Since March 16, 1999 to August 2002 he was under control. The state was stable. Now the patient moved to Donetsk region (data on 2003) Patient Z-va Yevgenia Dmitrievna, 1956 year of birth Diagnosis: right breast cancer Treatment: 19/06/1999 surgery: sectoral right breast resection. The patient is not subjected to specialized methods of treatment because of infarct. Since June 1999 She received 3 Flaraxin courses. At present she feels well, relapses and instant metastasis were not found (data on 2003). Patient K-esh Vera Ilyinichna, 1922 year of birth. Diagnosis: left breast cancer, IV stage, IV clinical group, metastasis into breast skin, axillary lymphatic ganglions, lymphatic ganglions of mediastinum. Specialized methods are forbidden because of the Mts spreading process. Left breast is practically full of neoplasm, melted to ribs, blood with pus are excreted from the wound in breast. Treatment: since March 1998 She received 3 Flaraxin courses the wound epithelized, axillary lymphatic ganglions and lymphatic ganglions of mediastinum disappeared, breast became soft and flexible. In July 1999 She was operated left breast gland was distracted. At the present the state of the patient is good. No relapse. (data on 2003) Patient N-va Lubov Alexandrovna, 1936 year of birth Diagnosis: right breast cancer T4N1M0 Treatment: received palliative chemotherapy course, due to sharp worsening of her state the treatment by chemotherapeutic preparations was not possible. From 24.09.2001 She received 3 Flaraxin courses. Right now her situation is stable. (data on 2004). Patient Sh-ko Antonina Vasilyevna, 1941 year of birth. Diagnosis: left breast cancer, metastasis into axillary lymphatic ganglions, cancerous intoxication, cachexia of the 1st stage. Objective: in the outer upper quadrant of the left breast a dense node with size of 6x8x10cm3 was found, which is tightly melted to skin. Treatment She received 3 Flaraxin courses from April 1999, after 3 courses axillary lymphatic ganglions resolved, the dense node diminished in size. The patient received one more Flaraxin course the dense node softened and was undetectable by palpation. The patient feels well. The state is stable, she works (data on 2003) Patient P-va Valentina Grigoryevna, 1949 year of birth. Diagnosis: left breast cancer, metastasis into left axillary lymphatic ganglions. The patient found the neoplasm herself, she was observed in oncological dispensary for 2 years, She refused to the proposed surgery, because her mother and sister died from identical operation Treatment: She received 6 Flaraxin courses from 10.07.1997 together with boligolov and tomaxifen. Left lymphatic ganglions disappeared, the neoplasm decreased in size. Until now the patient feels well, and still refuses the operation (data on 1999)
47
Patient N-va Irene Victorovna, 1959 year of birth. Diagnosis: right breast cancer, metastasis into lower sacral spine IV stage, IV clinical group. Treatment: From 01.11.1998 She received 4 Flaraxin courses general state is relatively satisfactory. The bleeding wound is epitalized. The neoplasm decreased in 1/3 of the previous size. Pain intensity decreased (data on 2001). Patient G-va Zinaida Savelievna, 1937 year of birth. Diagnosis: Melanoma of the neck skin on left side. Refused to do the surgery. Objective: in the neck area a traumatized pigmentary spot is found, lymphatic ganglion is increased up to the size 3x2cm2 in supraclavicular area. Treatment: After 3 Flaraxin courses the lymphatic ganglion disappeared, the pigmentary formation decreased in size, disappeared perifocal inflammation. Since May 1997 up to the present time the patient feels well, metastatic spreading is not found, the patient lives in Murmansk, Russia (data on 2000). Patient G-chuck Vasily Demidovich, 1943 year of birth. Diagnosis: pancreatic cancer, metastasis into lever, retroperitoneal and para-aortic lymphatic ganglions, intoxication, cachexia of the 2 stage, pronounced pain syndrome. Treatment: She received radial therapy and chemotherapy one course with no prominent effect. She received 3 Flaraxin courses intravenously in parallel detoxication and normalization therapy was done. The general state of the patient improved, the appetite restored, pain in abdominal disappeared, interest to life appeared. The patient continues to work (data on 1999). Patient I-yev Vladimir Petrovich, 1957 year of birth. Diagnosis: right lung cancer, metastasis into left supraclavicular lymphatic ganglions. PHC: glandular carcinoma. Treatment: He received chemotherapy without effect. He received 3 Flaraxin courses. His state is satisfactory, appetites is good, walks much (data on 2000) Patient T-iy Vladimir Alexandrovich, 1924 year of birth. Diagnosis: left lung cancer T3NxMx of the II stage. Treatment: Since 1998 He received 5 Flaraxin courses in parallel with restorative treatment. General state is satisfactory, pains in thorax disappeared with coughing and dyspnea, works at the summer cottage (data on 2003) Patient S-yeva Yekaterina Dmitriyevna, 1917 year of birth. Diagnosis: left lung cancer, metastasis into left lung root. The diagnosis was stated in 1998 in September. Treatment: Specialized methods of treatment are forbidden because of the age and presence of concomitant pathologies. She received 3 Flaraxin courses, after that dry hacking cough stopped, pain in thorax disappeared, the appetite improved. She lived 3 years and 4 months and died of extensive insult. Patient A-ko Petr Nickonorovich, 1940 year of birth. Diagnosis: left lung cancer, metastasis into mediastinal lymphatic ganglions. PHC: adenocarcinoma. Treatment: He received 5 Flaraxin courses, cervical supraclavicular lymphatic ganglions disappeared, dyspnea stopped, voice recovered. The patient lived 3 years and 10 months. Patient A-yev Alexey Andreyevich, 1933 year of birth. Diagnosis: left lung cancer, metastasis into mediastinal lymphatic ganglions, cancerous intoxication, cancerous cachexia. PHC: planocellular cancer. The patient suffers since November 1998. Treatment: Specialized methods of treatment are forbidden because of the process spreading. From March 1, 1999 He received 3 Flaraxin courses. The temperature normalized, coughing stopped. Pain in thorax decreased. On X-ray control of thorax organs: mediastinal is free, left lung neoplasm became smaller on 2/3 and takes shape as calcenat (data on 2003). Patient B-ko Svetlana Ivanovna, 1969 year of birth. Diagnosis: Endometriosis of the uterus and ovaries, uterine fibroids with submucous mucous nodes, ovarian cyst. PHC: glandular hyperplasia of the endometrium of mixed type. Treatment: operative treatment is suggested, which the patient categorically denied. 21.06/2001 the course of flaraxin is prescribed. 3 courses are carried out. General state was improved, oaria cyst resolved, fibroids twice decreased (data on 2004). Patient O-ka Ekaterina Makarovna, 1927 year of birth. Diagnosis: cervix of the uterus cancer. PHC: highly differentiated adenocarcinoma with germination into muscular layer. She complaints on abundant secretions from vagina with the admixture of blood and pyorhea. Treatment: she refused hospitalization for family reasons. After 3 courses of Flaraxin treatment general state improved, appetite became better, pain in the lower area of abdomen disappeared, secretions from vagina stopped. On Ultrasound-control of abdominal cavity organs and small pelvis is stabilization of the process is prominent. The operational treatment is suggested again, but the patient refused (data on 2004).
48
Patient V-kaya Maria Yefimovna, 1921 year of birth. Diagnosis: cervix of the uterus cancer, IV stage, metastasis into neighboring organs. PHC: highly differentiated adenocarcinoma. She complaints on bloody secretions from vagina. Treatment: The patient received 4 Flaraxin courses. The bloody secretions from vagina stopped, asthenia disappeared, the appetite became better. The treatment was started in 1999, in May 2002 the state of the patient is satisfactory (data on 2004). Patient R-yak Anna Konstantinovna, 1944 year of birth. Diagnosis: oaria cancer T3N1M0, IV stage, IV clinical group. Treatment: After 3 courses of chemotherapy the disease continued to progress, metastasis into the left lung, ascites, cancerous intoxication. In 1998 (October) Flaraxin treatment was prescribed. 5 courses of Flaraxin was received. The patients state was satisfactory, able to work. The patient moved to Archangelsk, Russia to her daughter (data on 2003). Patient L-aya Ludmila Vladimirovna, 1959 year of birth. Diagnosis: uterus fibroids, ovarian cysts, combined with endometriosis. She had periodic pains in abdomen, strong bleeding during menses. Treatment: She received 3 Flaraxin courses the state of the patient improved, the pain stopped, menses became normal (data on 2006). Patient V-va Vera Kuzminichna, 1951 year of birth. Diagnosis: rectal cancer, metastasis in liver, retroperitoneal lymphatic ganglions T4N3M1. Treatment: In January 2001 surgery, laparotomy with holostomy placement. In February 2001 Flaraxin treatment was started, She received 3 Flaraxin courses general state of the patient improved, walks much, the appetite is good. In November 2002 she moved to Russia (data on 2004). Patient Ch-va Ludmila Danilovna, 1940 year of birth. Diagnosis: Recurrent adenocarcinoma of the rectum, adhesive disease. Treatment: In 1992 sigmoid intestine resection in USA, in 1993 left kidney resection, operation in 1996 resection of the colon ascending area in Moscow, Russia. In 1997 Faraxin treatment was started She received 3 Flaraxin courses, until now she feels well, living an active lifestyle (data on 2006). Patient I-ko Victor Alexandrovich, 1936 year of birth. Diagnosis: cancer of the lower rectum, metastasis into prostate. Treatment: The course of chemotherapy was prescribed, but it was interrupted because of sharp worsening of the patient state. In July 2001 Flaraxin treatment was started, He received 4 Flaraxin courses. The state of the patient at present is satisfactory (data on 2005). Patient O-va Nina Ivanovna, 1954 year of birth. Diagnosis: right breast cancer. Treatment: In February 1998 the patient underwent the surgery radical mastectomy. She received radial therapy, 5 courses of chemotherapy. In March 1999 the process spreading was marked: metastasis into right lung, mediastinal lymphatic ganglions, cancerous intoxication and cachexia of the 1st stage. She received 3 Flaraxin courses, after the 1st Flaraxin course she felt improvement in her state, coughing diminished. After 3 Flaraxin courses coughing stopped. The patient was able to sleep in bed, start to do housework. In August 2000 the state of the patient remained satisfactory, but coughing appeared again. In February and March 2001 She received 2 more Flaraxin courses until now the state of the patient remains stable (data on 2003). Patient N-ev Anatoly Alexandrovich, 1947 year of birth. Diagnosis: Cancer of the stomach output, metastasis into abdominal cavity, cancerous intoxication and cachexia of II stage. Treatment: In 1997 (November) surgery fistulization. This case was considered as non-operational because of the process spreading, special methods of treatment are forbidden. In March 1998 Flaraxin treatment was started. After the 1st course general state improved, gained weight 2 kg, continues to work as a driver. As a whole He received 3 Flaraxin courses. In December 2001 the patient came for control consultation the state of the patient remained stable, he continued to work. The patient did not come for the last consultation because he went to Moscow (data on 2002). Patient Sh-aya Alexandra Markovna, 1936 year of birth. Diagnosis: left breast cancer, metastasis into mediastinal lymphatic ganglions, neoplasm decomposition. PHC: cyst adenocarcinoma. Treatment: In May 1996 she found an induration, but she did not have contact with doctors, practiced autotherapy. In August 1997 she visited oncology dispensary, where she was refused in specialized methods of treatment because of the process spreading and neoplasm decomposition. Objective: left breast is sharply melted to ribs; tumor wounded with abundant detachable pus with blood. She received 3 Flaraxin courses, the wound epithelized, the neoplasm diminished twice in size, two axillary lymphatic ganglions resolved. In 2000 the patient came for consultation with complaints on asthenia, tussiculation, temperature 37,3C. X-ray diagnoses that left lungs have inflammation. She was hospitalized into the stationary. After antibiotics course she was discharged from hospital in satisfactory condition (data on 2001).
49
Patient K-ko Vladinir Makarovich, 1918 year of birth. Diagnosis: Rectal cancer. PHC: differentiated adenocarcinoma. Complaints on asthenia, loss of weight, pain in the lumbar spine, liquid stool mixed with blood, adversion to meat. Treatment: From 21.06.1997 to 19.10.1998 He received 8 Flaraxin courses. His state improved greatly and remained stable satisfactory up to 2000. He died in 2000 infarct. Patient P-ko Maria Andreyevna, 1926 year of birth. Diagnosis: sigmoid intestine and rectal cancer, pathological fracture of the right cervix thigh. PHC: adenocarcinoma. Persistent pain in the abdomen and lower spine. Treatment: in oncology dispensary the case was considered as nonoperational because of the process spreading, special methods of treatment are forbidden. After the 1st Flaraxin course her state improved. As a whole She received 6 Flaraxin courses. Her state is stable; she is doing housework (data on 2006). Patient L-va Natalya Nikolayevna, 1980 year of birth. Diagnosis: Pituitary tumor with suproselyarnym growth. Tumor was not operable. Radiation and Chemiotherapy were not applicable. Her complains: menses disorder. Treatment: After 3rd Flaraxin course her state is satisfactory, vision was restored, headaches disappeared as well as giddiness, the menses began regularly, abundant and in time (before menses 10 months were absent). After 4th Flaraxin course in 1999 she was consulted in the Institute of Neurosurgery in Kiev neoplasm minimized, the girl was operated intranasally. She finished school with the gold medal. She entered the institute (data on 2006). Patient K-ov Vyacheslav Alexandrovich, 1993 year of birth. Diagnosis: Neuroblastoma of retroperitoneal space with germination into the body of spine L3-L4. Treatment: He visited our center in 1997, before surgery and 3 courses of chemotherapy in Kiev were done without improvement. From September 1997 to March 1999 He received 7 Flaraxin courses. In May 1999 over his mother informed us that He feels well and visiting his grandmother on the countryside for a month. In January 2000 He came for consultation: the state was satisfactory, no complaints, in lungs the breathing is vesicular, abdomen is painless. After examination on NMR pathological changes was not detected. 30.08.2000 He came for consultation complaints only on irregular defecation, the patient got the 2nd invalidity group, studying at home is recommended. From the 4 Flaraxin course the treatment of the child in the Centre was free of charge (data on 2004).
50
CONCLUSIONS
I.A.Egorov, A.G.Serbin, V.V.Rossikhin, A.V.Artemov, V.A.Sorokin, E.I.Oleynik, V.P.Shetilov, L.P.Pelichova, I.G.Vakaryuk. Scientific and treatment center for cancer curing PHOENIX (http://www.stccc-phoenix.com) National University of Pharmacy (NUPh) of Ukraine (http://www.pharm.kharkiv.edu/) Kharkiv Medical Academy of Postgraduate Education (http://med.edu.ua/en) Filatov Institute of eye diseases and tissue AMS of Ukraine (http://www.filatov.md/eng/)
1.
FLARAXIN should be recommended to the wide clinical application as a cytostatics drug, which proved to be effective in patients with cancer of the following organs: cerebrum (brain) cancer, melanoma, melanoblastoma, breast cancer, mammary gland cancer, lungs cancer, stomach cancer, bladder cancer, colorectal cancer, colon cancer, uterus cancer, cervix cancer, ovaries cancer, neck of womb and womb cancer, bowels cancer, prostate gland, adenoma, mediastinal cancer, non-malignant neoplasm, improving general state of patients, not suppressing hemopoiesis and does not have an adverse effect on CNS, does not disrupt the function of the vitally important organs (liver, kidneys, cardiovascular system (CVS)) , with very rare exception of side effects. FLARAXIN can be administered not only to advanced cancer patients, but also for curable patients in combination with the radiological, and in combination with chemo-regimens and surgery (as prevention of cancer recurrence).
2.
The clinical administration of drug FLARAXIN is recommended by us in the following cases: 1. The largest benefit from FLARAXIN is achieved in patients with the pretumorous proliferating processes, and also in the persons, with the minimum tumor process, after the radical surgical treatment, when it is necessary to conduct the restoration of the anti-tumor resistance of organism and its homeostatic mechanisms; FLARAXIN combined together with poly-Chemotherapy proved to be highly effective among the patients with heavy cancer process due to its specific anti-cancerous action and protective properties. Treatment with Flaraxin can be done in mono and complex therapy; moreover FLARAXIN can be administered before Poly-Chemotherapy, in periods between treatment cycles of Chemotherapy, and for stabilization after positive results achieved by standard therapy due to its minimum toxicity and ability to stop metastatic spreading. Flaraxin exists in intravenous injections, capsules, tablets for oral and cones (suppository) for rectal and vaginal application.
2.
FLARAXIN is compatible with many anti-cancer drugs according to its chemical properties, with exception of those that contain iron (Fe) inside, because Flaraxin can form a complexes with iron (Fe). Application of FLARAXIN to Chemotherapy is able to decrease side effects: Cardiotoxicity, caused by the activation lipooxygenases with characteristic of the antibiotics of the anthracyclines line; Neurotoxity is similar to the preparations of the [vinka]- class (Vincristine, Vinblastine); Pa-pyramidal disorders and syndrome of orthostatic hypotension are similar to Fluorineuracil; Myelotoxic effect and immunodepression are similar to alkylating preparations.
51
Summarizing 8 years of our work experience we suggest to include FLARAXIN in different treatment procedures of oncological patients.
The treatment methods of the oncological patients are accompanied by powerful immune suppression, which suppresses the function of immune system in considerable extent, locking the vicious circle of the tumor process. With the administration of FLARAXIN before the chemotherapy it is necessary to consider some of its special features. Thus, for instance, under Flaraxin influence on tumor cells they become more vulnerable to the factors of natural antitumor immunity and anti-tumor cytostatics. Therefore for the more effective treatment by FLARAXIN it is necessary to do analysis of initial immunobiochemical indices of patient, with aim to compare them after treatment by Flaraxin. FLARAXIN should be assigned at the low level of the cytotoxic activity of the natural killers (lower than 40% - it is compulsory, from 50 to 55% - preferably); with the presence of initial non-protein SH-groups, in the blood serum (spontaneous dysproteinemia with the autoimmune aggression); and also during the disturbance of the oxidation-reduction (SH-SS) potential of serum proteins. Frequently all these disturbances are combined with each other. If 8 assigned injections of FLARAXIN normalized the existing disturbances, noted above, then it is possible to begin chemotherapy. In case the optimal immunobiochemical indices are not achieved yet after 8 injections however background dynamics is positive, i.e., it is indicated to assign additional 8 injections. If it is not possible to perform at least one of the given immunobiochemical tests then It can be seen by the clinical picture during treatment course. Thus, with the noticeable subjective improvement after the first 8 injections of FLARAXIN, it makes sense to continue with additional 8 injections. If no subjective signs of improvement are seen, it is suggested to stop the treatment. If patient experiences intolerance to the drug, it is necessary to stop injections. In such cases, it is suggested to combine FLARAXIN together with histamines drugs that is able to prevent allergic reaction of organism (Kenolog, Suprastin, Chloropyramine, etc) or to conduct several sessions of Plasmapheresis. It is desirable to begin immediately with treatment by FLARAXIN after the end of Chemotherapy, especially if the immunobiochemical indices reduction is seen. In case of second-line Chemotherapy is planned, and then FLARAXIN should be given to achieve a maximum improvement of immunobiochemical indices. Low immunobiochemical indices are the main indication to assign extra 1 or 2 additional courses of Flaraxin. Substantially the cancer therapy is the immunological problem which is based on the formation of antibodies, in response to the complex antigens of the oncologic-associated proteins and medicinal substances. If immunobiochemical indices are clearly reduced, then the use of plasmapheresis is an important component of medicinal therapy and it is desirable to assign the treatment after repeated courses of poly-Chemotherapy. In this case the determination of the initial non-protein SH-groups in the blood serum is most informative. Their appearance testifies about necessity for the assignment of Plasmapheresis. Function of plasmapheresis can sometimes be replaces by treatment with FLARAXIN between the chemotherapy courses, since FLARAXIN is able to have link with immune complexes. Plasmapheresis is necessary if negative immunobiochemical indices (especially non-protein SH-groups) are registered after combined treatment of chemotherapy with FLARAXIN. Number of plasmapheresis courses can vary depending on the level of the immunological disturbances (disappearance of the SH-groups serves as control indication). In case of fractional plasmapheresis is applied then 5 up to 10 sessions are necessary together with blood purification (500 ml each session).
Assigning of FLARAXIN strengthens the chemotherapy effect, mover, in case the drugs transference is satisfactory then the dose reduction is not advisable. Lower dose of chemotherapy with FLARAXIN combination are recommended in patients with diseases which diminish the effect of intensive chemotherapy. When FLARAXIN is assigned to heavy cancer patients, Chemotherapy should be given at lower doses (1/5 -1/10) in order to improve oncolytic action of FLARAXIN. In this case it is recommended to assign the chemical drug not used to the patient before treatment with FLARAXIN. The duration of the joint application of FLARAXIN and the chemical preparations must be determined by clinical picture and immunobiochemical indices of patient. If each such course is accompanied by the normalization of immunobiochemical indices, then the combination of chemotherapy and FLARAXIN should be continued. Experience suggests 1-2 courses of FLARAXIN combined with chemotherapy plus one additional course after the end of chemotherapy in the subsequent year as an ideal scheme. The application of FLARAXIN is not expedient in case of the following diseases: blood cancer, sarcoma of bone tissues, extensive liver cancer and extensive kidneys cancer. FLARAXIN is effective with the following diseases: brain cancer, melanoma, melanoblastoma, breast cancer, lung cancer, mammary gland cancer, uterus cancer, cervix cancer, ovaries cancer, bowels cancer, neck of womb cancer, womb cancer, prostate gland cancer, adenoma, mediastinal cancer, colorectal cancer, colon cancer, stomach cancer, bladder cancer, non-malignant neoplasm, which are equivalent to 90% of a total quantity of oncological diseases. FLARAXIN is most effective in the cases of the small tumors, when vital organs (liver, kidneys) are partly defeated. In these cases the complete reduction of tumor can be reached.
52
Head of the Botany Department of National University of Pharmacy of Ukraine Head of the Urology Department of Kharkiv Medical Academy of Postgraduate Education Professor of the Department for Drugs Technology of National University of Pharmacy of Ukraine Docent of the Oncology Department of Zaporizhzhia Institute for Advanced Medical Training Docent of the Oncology Department of Odessa SRI (Scientific Research Institute) of Ophthalmology im.Filatova Oncologist Oncologist Oncologist
Prof. Doctor of pharmacy A.G.SERBIN
Prof. DMS V.V.ROSSIKHIN
Doctor of pharmacy I.E.EGOROV
DMS V.A.SOROKIN
DMS A.V.ARTEMOV V.P.SHETILOV E.I.OLEYNIK L.P.PELIHOVA
53

Flaraxin

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FLARAXIN IS EFFECTIVE IN 90% OF ONCOLOGIC DISEASES

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INFORMATION ABOUT STCCC PHOENIX

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Our address : Svobody sq. 7, office 378, 61022-Kharkiv, Ukraine

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THE HISTORY OF THE FLARAXIN

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III-rd AND IV-th STAGE OF MALIGNANT NEOPLASM TREATMENT

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FLARAXIN APPLICATION EFFICIENCY IN DIFFERENT CASES WITH CANCER.

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1 2 3 4 FLARAXIN injec- tions Cones with FLARAXIN

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FLARAXIN Questions and answers

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Doctor of Medical Science - I.P.Loboda.

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List of patients with melanoma (I phase)

Remission period after FLARAXIN 13 14 Alive from 1 08.1990

1 course 15days, 2 course 20days 21days

Intravenously 1,8 mg/kg

Without changes No marks

Intravenously 4 mg/kg 14 days, 2 mg/kg 12 days

Alive from 1 20.12. 1990 1

Vein elbow Irritation on 3rd course of the treatment

Full Regression of neck node. After 2nd course operation

Feels without changes Feels without changes

Alive from 6 15.02.1991 Alive from 7 23.01.1991

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Melanoma of 3 concha of auricle, Mts in lymph nodes of neck

17 days + surgery 20 days

Treatment endured Alive from satisfactorily 10.03.1991 . 4-

15 Gutsulyak P.V. male 32

20 days -----20 days 19 days + surgery 17 days

Melanoma of left 3 shank skin, Mts in lungs

Melanoma of left 3 buttock with generalization of the process

female Melanoma of the 3 back skin

Intravenously 2 mg/kg infiltration into tumor nodes Flaraxin Intravenously 2 mg/kg

Intravenously 2,3 mg/kg

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16 days + unnoticed Prophylactic course

1*20 days unnoticed after 3weeks 2 mg/kg 15 days

Alive from 2 . 20.02.1991

female Melanoma of mammary gland skin

Alive from . 04.04.1991 04

Patients quantity Patients with recurrence after

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Doctor of Medical Science - V.S.Protsick.

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7 8 2 mg/kg 20 vials, 20 days 2 mg/kg 20 vials, 20 days

Zignel Galina Vasilievna story913/92

2 mg/kg 20 vials, 20 days