CHEMOTHERAPY OF

CANCER
SUBMITTED BY

SYAMA . J.S

ROLL NO :15

2ND SEM

M PHARM PHARMACOLOGY
 CANCER WORLD CANCER DAY
FEBRUARY 04

Cancer is a term used for diseases in which abnormal cells divide

without control and are able to invade other tissues. Cancer cells can spread to other parts
of the body through the blood and lymph systems.

Cancer is a class of disease characterized by Progressive, Persistant, Perverted,

Purposeless and uncontrolled Proliferation of tissues Dedifferentiation, Loss of function,
Invasion to local tissues, Spread or metastasis to other parts of the body

o The medical term for tumor or cancer is Neoplasm, which means a relatively
autonomous growth or uncoordinated cell proliferation of body tissue.
o Excessive study of neoplasm and its development diagnosis and treatment is called
Oncology.
 CHARACTERISTIC OF CANCER
Cancer arises as a result of a series of genetic and epigenetic changes, the main genetic
lesions being:
• inactivation of tumour suppressor genes
• the activation of oncogenes (mutation of the normal genes controlling cell division and
other processes).
Cancer cells have four characteristics that distinguish them from normal cells:
• uncontrolled proliferation
• loss of function because of lack of capacity to differentiate
• invasiveness
• the ability to metastasise.
Cancer cells have uncontrolled proliferation because of changes in:
• growth factors and/or their receptors
• intracellular signalling pathways, particularly those controlling the cell cycle and apoptosis
• telomerase expression
• tumour-related angiogenesis 4
 NORMAL CELL VS CANCER CELL
NORMAL CELL CANCER CELL
 Mortal (die ~ 50 division)  Immortal (divide indefinitely)
 Contact inhibition  Loss of contact inhibition
 Stay bound together  Can easily detach from each other
 Controlled cell death (Apoptosis)  Unresponsive to apoptosis
 Controlled cell division  Increased rate of cell division
 Control of angiogenesis  Unregulated angiogenesis
 Mature in to functional cells  Do not mature in to functional cells
Nomenclature
On the basis of parenchymal cells they are derived
not all tumors are cancerous; tumours can be Benign and Malignant.
• Benign tumours
aren’t cancerous, They can often be removed and in most cases,
they do not come back, cells do not spread to other parts of the body
• Malignant tumours-
are cancerous , cells can invade nearby tissues and spread to other parts of the
body(Metastasis)
Beningn Malignant

Slow growing Rapidly growing

Grow only locally Invade to neighboring tissue
Cause less damage to host Cause eventual death of host
Spherical/Ovoid Irregularly shaped dividing cells
Encapsulated Un-capsulated
Non-Invading Invading
No or few symptoms Associated with pain and disability
Does not cause metastasis Metastasis
Suffix “ oma” Eg :Fibroma Suffix “ Carcinoma” or “Sarcoma”
Removal is not diificult, No recurrence of Removal is difficult, tend to recur after
tissue apparent removal
 Examples of Benign tumors(Non-Malignant)
Papilloma - A projecting mass on the skin (for example a wart)
Adenoma - A tumour that grows in and around the glands.
Lipoma - A tumour in fatty tissue
Osteoma - A tumour originating in bones
Myoma - A tumour of muscle tissue
Angioma - A tumour composed of small blood or lymph vessels(birthmark)
Nevus - A small skin tumour of one variety of tissues (mole)
Most common cancers in Children and Adults
Children Adults
 Leukemias - Acute lymphocytic  Lung
 Brain and other nervous system - Neuroblastoma  Breast(carcinoma)
 Lymph node cancers - Lymphomas  Colorectal
 Bone - Osteosarcoma  Prostate
 Soft tissue sarcomas - Rhabdomyosarcoma  Skin(melanoma)
 Kidney - Wilms tumour
 Eye - retinoblastoma
 Adrenal gland - Adrenocortical carcinoma
 Types of cancers( Based on origin)
o Carcinoma
Cancer that begins in the skin or in tissue that line or cover internal organs.
Adenocarcinoma(pituitary, Adrenal glands) Basal cell carcinoma, Squamous cell carcinoma,
Transitional cell carcinoma.
o Sarcoma
Cancer begins in bone, cartilage, fat, muscle, blood vessels or other connective or supporting
tissue.
o Lymphoma & Myeloma
Cancers that begin in the cells of the immune system
o Leukemia
Cancer starts in blood-forming tissue such as bone marrow and often accumulate in the blood
stream.
o Central nervous system cancers
 Cancers that begin in tissues of the brain and spinal cord
o Germ cell cancer-
Pluripotent Germ cells , testicle and ovarian cancers
o Blastoma-
Cancers derived from immature precursor cells embroyonic tissue
SIGNS AND SYMPTOMS
1Change in bowel or bladder habits –Colorectal cancer
2.A sore that does not heal
3.Unusual bleeding or discharge
4.Thickening or lump in the breast, testicles, or elsewhere
5.Indigestion or difficulty swallowing
6.Obvious change in the size, color, shape, or thickness of a wart, mole, or mouth sore
7.Nagging cough or hoarseness, Bronchous block – Lung Cancer
8. Persistent fever- Hodgkin disease, leukemia , cancer of liver and kidney
9.Difficult or painful to swallow- Narrow of esophagus-Esophageal cancer
Causes of cancer(Carcinogenesis)
EXTRINSIC FACTORS
1. Physical agents –
UV and ionizing radiations(x-ray, gamma ,alpha & beta rays) cause cancer
 Mutagenic effect
Prolonged exposure to asbestos.
Powdered metallic cobolt, nickel and crystalline silica (non fibrous particulate matter)
Naturally occurring mineral fibres –cause mesothelioma
Eg: Leukemias, Skin, Lung, Breast, Osteosarcoma, Thyroid cancer.

2. Biological Agents-
a) Bacterial Agents: Peptic ulcers and chronic gastritis left untreated for a long time leads to
gastric cancer.
b)Fungal Agents: Aspergillus flavus releases aflatoxins in stored food and grains
contaminated food is consumed (especially by Hepatitis B virus infected patients) it
leads to Heptocellular carcinoma.
c) Viral Agents: Human pappilloma virus-Cervical cancer
Epstein- barr virus-Nasopharyngeal carcinoma
Kaposi’s sarcoma herpes virus – Kaposi’s sarcoma
Hepatitis B & C virus – Hepato cellular carcinoma
Human T- cell leukemia virus – T cell leukemia
3. Chemical Agents
Alkylating agents, Acylating agents, Polyaromatic Hydrocarbons, Aniline dyes , Arsenic,
Anthracenes , Acetyl imidazole , dimethyl carbamyl chloride ,Benzene
Tobacco smoke , nicotine
Alcohol-Liver and digestive tract cancer
Coaltar
INTRINSIC FACTORS

1.Genetic and Heredity factors :

Genetic inheritance –Breast carcinoma , Retinoblastinoma
eg: inherited mutation in the genes BRCA 1 and BRCA 2 with more than 70% risk of
breast and ovarian cancers
2.Diet and Habbit , Exercise:
Rich in fats, low fibre content and stored grains
Physical inactivity , Obesity , Alcoholism , Chewing tobacco and betel nut(pan
masala . Gutka)
3.Hormones and Drugs :
 Taking excessive oestrogen during the time of pregnancy promote cell proliferation
 Hormones act as agents in Breast , Endometrium ,Prostate, Ovary and testis.
 GENES IMPLICATED IN CANCER
• Genes can be mutated in several ways. The simplest type of mutation involves change in a
single base along the base sequence of a particular gene.

• In other cases one/more base may be added or deleted and sometimes large segments of DNA
molecule are accidently repeated , deleted or moved

• Damaged genes are implicated in the development of cancer and are called ONCOGENES.
Oncogene are gene, whose presence in certain form and or overactivity can stimulate the
development of cancer.
• They contribute to the development of cancer by instructing cells to make protein that
stimulate excessive cell growth and division

• Types of genes
1. The growth promoting genes

2. Growth inhibiting cancer suppressing gene

3. DNA repair genes

• The mechanism by which proto-oncogenes are transferred into oncogene is brought about in
two ways

1.By change in the structure of the gene . This result in the synthesis of an abnormal gene product
(oncoprotein) which has an abnormal function.

2. By change in the regulation of gene expression . This result in increase or inappropriate

products of the growth factor

• These structural and regulator changes occurs because of,

a) Point mutation :– bring about structural changes in gene

b) Chromosomal translocation :- rearrangement of genetic material brought about by

chromosomal translocation results in over expression of proto oncogene
c) Gene amplification ;-

the amplification of DNA sequences in proto oncogene can lead to over expression
Oncogenes arise from the mutation of proto oncogene , they resemble oncogenes in that they
code for the production of protein involved in growth control

• Oncogene code for an altered version of these growth control protein oncogene cause a cell
growth – signaling pathway became hyperactive.

2.TUMOR SUPPRESSOR GENE (TSG)

Absence TSG can lead to cancer

If a pair of tumor suppressor genes are either lost from a cell or inactivated through mutation,
their functional absence might allow cancer to develop.
TSG are family of normal genes that instruct cells to produce protein that restrain cell growth
and division.

The loss of such protein allows cells to grow and divide in an uncontrolled fashion

One particular tumor suppressor gene code for aprotein called P53 that can trigger cell suicide
(apoptosis)

3.DNA REPAIR GENE

“code for protein”

 The normal function is to correct errors that arise when cells duplicate their DNA prior to cel
division.

 Mutation in DNA repair gene leads to failure in repair.

Eg . People with xeroderma pigmentoscem have an inherited defect in DNA Repair gene.
• Cancer may begin because of the accumulation of mutation involving oncogene, TSG and
DNA repair gene

e.g colon cancer begin with a defect in TSG that allow excessive cell proliferation. The
proliferating cells acquire additional mutation involving DNA repair gene and other TSG, and
many other related gene – finally leads malignant metastatic cancer

• Mutation also seen in the genes that activate and deactivate carcinogens and in those that
govern the cell cycle, cell senescence, cell suicide (apoptosis), cell signaling and cell
differentiation.
DIAGNOSIS OF CANCER

Biopsy - involves histological examination by a pathologist of a piece of tissue.

 Imaging techniques – CT scan, MRI, UTZ
 Laboratory test
 Tumor markers(produced by cancer)
CA15-3 - Breast cancer.
CA19-9 - Gastrointestinal tumours.
CA-125 - Ovarian cancers.
PSA (prostate specific antigen)- Prostate cancers.
• TREATMENT OF CANCER
CHEMOTHERAPY
• Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs
(chemotherapeutic agents) as a part of standardized regimen.

• Traditional chemotherapeutic agents act by killing cells that divide rapidly, a critical
property of most cancer cells.

• Targeted therapy is a form of chemotherapy that target specific molecular differences

between cancer and normal cells .
The efficacy of chemotherapy depends on the type of cancer and the stage.
In combination with surgery, chemotherapy has proven useful in cancer types
including breast cancer, colorectal, pancreatic cancers, estrogenic sarcoma etc
The effectiveness of chemotherapy is often limited by its toxicity to other tissues in
the body.
Even when chemotherapy does not provide a permanent cure, it may be useful to
reduce symptoms
• Adjuvant chemotherapy: –
Chemotherapy given after surgery or irradiation to destroy micrometastasis &
prevent development of secondary neoplasm.
•Neo-adjuvant chemotherapy: –
Chemotherapy given before surgery or radiotherapy in order to diminish the
volume of large primary neoplasm
RADIATION
• Radiation therapy involves the use of ionizing radiation in an attempt to either cure or
improve symptoms. It works by damaging the DNA of cancerous tissue, killing it.
• The radiation is most commonly low energy X-rays for treating skin cancers , while high
energy X-rays are used for cancer within the body.
• Radiation is typically used in addition to surgery and or chemotherapy’
• Iodine -131(thyroid cancer),
Iridium-192(Breast cancer)
 SURGERY
• Surgery is the primary method of treatment for most isolated , solid cancers
• In localized cancer, surgery typically attempt to remove the entire mass along with, in
certain cases, the lymph nodes in the area.
• Not metastasized cancers prostate, breast or testicular cancers
PALLIATIVE CARE
 Palliative care refers to treatment that attempts to help the patient feel better and may be
combined with an attempt to treat cancer.
 The primary goal is to improve quality of life.
 Palliative care include action to reduce physical, emotional, spiritual and pyscho-social
distress
TOXIC EFFECTS OF ANTICANCER DRUGS

1.General toxicity
a) Bone marrow suppression(myelosuppression):
Leukopenia ,agranulocytes,thrombocytopenia and aplastic anaemia. Infection and
bleeding is common.
reduced by –platlet transfusion
Granulocyte Colony stimulating factor(G-CSF)
Erythropoietin
Bone marrow transplantation
Using bone marrpw-sparing drugs L-asparginase,bleomycin,
cisplatin,vincristine
b) Immunosuppression
Decreased lymphocytes ,patients are prone for oppurtunistic diseases with
fungi, bacteria,viruses,parasites etc
C) GIT
 Nausea and vomiting(stimulation of CTZ)
 Cisplatin -emetogenic potential(antiemetics 5-HT3 antagonists- Ondansteron)
 Stomatitis, Diarrhoea,GI bleeding,shedding of mucosa,Ulcers in gut mucosa
 Drugs causing Mucositis- Bleomycin ,Actinomycin D, daunorubicin
,doxorubicin
d) Skin and Hair
Alopecia (loss of hair) due to damage of hair follicles,reversible on stoppage of
therapy. Dermatitis and skin rashes
e) Gonads
oligozoospermia and infertility in males, Amenrrohea and infertility in females
f) Foetus
During pregnancy-Abortion ,Foetal death, teratogenesis
g) Carcinogenicity
Secondary malignancy
Development of leukaemia in patients with prolonged use of alkylating agent
h) Hyperuricaemia
Gout and urate stones in UT due to excessive cell destruction
Prevention: good hydration, allopurinol and corticosteroids
i) Mutagenicity
ANTICANCER DRUG CLASSIFICATION
1.Depending upon the MOA on the cell level
2 . CELL CYCLE SPECIFIC AND NON –SPECIFIC GRUGS
G1 phase (presynthetic phase)-Synthesis of enzymes and other cellular components needed for DNA synthesis
S phase (Synthetic phase):DNA synthesis takes place
G2 phase(premitotic phase)-Synthesis of cellular components for mitosis(proteins and RNA synthesis
M phase-Mitotic cell division takes place
G0 phase (resting phase)-Cells stop dividing temporarily or permanently
CELL CYCLE NON SPECIFIC CELL CYCLE SPECIFIC

Kills resting cells & dividing Kills actively dividing cells

cells
Cyclophosphamide • G1 – Vinblastine
• Chlorambucil • S – Methotrexate
• Metal complexes :Cisplatin 6-Mercaptopurine
• Antibiotics: Actinomycin-D 5-Fluorouracil
• L-asparaginase • G2 –Bleomycin
• Camptothecins: Topotecan Etoposide, Topotecan
Daunorubicin
• M – Vincristine
Vinblastine
Paclitaxel, Docetaxel
Mechanism and site of action of some chemotherapeutic drug
ALKYLATING AGENTS- Nitrogen mustard, Methyl hydrazines, Alkyl sulphonates,
Nitrsourea, Triazines , Platinum compounds
• Alkylating agents contain chemical groups that produce highly reactive carbonium ion
intermediates that can form covalent bonds with particular nucleophilic,substances in the cell.
• These ions are highly reactive with electron donors such as amine,hydroxy and sulfhydryl
groups.
• Prevent the cell division and protein synthesis.
• Pharmacologic action
Cytotoxic action
• Use
• Chronic myelocytic leukaemia
• Polycythaemia
• Toxicity-
Bone marrow toxicity
Mucosal toxicity- Ulceration
Alopecia
Neuro toxicity
a) Nitrogen mustards- Cyclophosphamide, Mechlorethamine, Chlorambucil
,Melphalan,Ifosfamide
1.Cyclophosphamide : MOA : It is a pro drug and activated in liver by CYP 450
Cyclophosphamide

Aldophosphamide

Phosphoramide Acrolein Mesna

Mustard (Toxic metabolite)
(cytotoxic effect) Causes Haemorrhagic cystitis
USES
combination with other anticancer agents in treatment of Hodgkin’s disease and non
hodgkins lymphoma
Burkitt’s lymphoma, Lymphatic leukaemia
Immunosuppressant effect
Neuroblastoma , retinoblastoma ,breast carcinoma, adenocarcinoma of ovaries
Non neoplastic condition
To treat graft rejection during organ transplantation
Rheumatoid arthritis
Nephrotic syndrome

Adverse effects
Haemorrhagic cystitis associated with dysuria and haematuria due to irritation of
bladder mucosa by acrolein
Mesna binds it and inactivates acrolein
Alopecia
Hepatic damage
Nausea and vomiting
2. Melphalan
Very effective in MULTIPLE MYELOMA ,Ovarian carcinoma, Breast cancer
Less irritant locally , less alopecia ,rarely renal or hepatic dysfunction
Nausea and vomiting less frequent
ADR
Bone marrow Depression (Myelosuppression)
Infections , diarrhoea and pancreatitis
3.Mechlorathamine(mustine)
First nitrogen mustard
Highly reactive and local vesicant
Use
Hematological cancers , lymphomas , solid tumors
Hodgkins as part of MOPP, CML, CLL
Adverse Effects
Anorexia,
nausea,
vomiting
Bone marrow depression, aplasia
Menstrual irregularities
4. Ifosfamide
Congener of cyclophosphamide
Longer half life than cyclophosphamide
Less alopecia and less emetogenic than cyclophosphamide
USE
Bronchogenic, Breast ,Testicular, bladder, head and neck carcinoma, Oesteogenic
sarcoma and some lymphoma, Used for germ cell testicular tumors
• ADR
Can cause hemorrhagic cystitis and severe neurological toxicity ,lethargy ,
confusion

5 ) CHLORAMBUCIL
Slowest acting and least toxic alkylating agent
Main action on lymphoid series produces marked lympholytic action
USE
Drug of choice for long term maintenance therapy of CLL (Chronic Myeloid
Leukaemia)
Non Hodgkins lymphoma
Immunosuppressant property
ADR
Pulmonary fibrosis, Hepatotoxicity, dermatotoxicity, Myelo suppression
• Miscellaneous alkylating agent- Thiotepa , Ethyleneimines and methylmelamins.

THIO-TEPA
Triethylene phosphoramide
High toxicity
USE
Rhabdomyosarcoma, breast cancer, Ovarian cancer
ADR
Infertility, Myelosuppression
• Platinum Coordination compounds – Cisplatin Cl NH3
CISPLATIN
• Non cell cycle specific killing Pt

Cl NH3

• Uses – Testicular cancer

Ovarian cancer
Other solid tumors: lung, esophagus, gastric
Bladder, hepatic , Head and neck carcinoma
Side Effects
Emesis , Tinnitus , deafness, Hyperurecemia
Nephrotoxicity
Peripheral neuropathy
Ototoxicity
ANTIMETABOLITE- Folic acid Analogue, Pyramidine analogue, Purine analogue

 Antimetabolites are structurally related to normal componente of DNA or of

coenzymes involved in the nucleic acid synthesis.

 These generally interfere with the availability of purine or pyrimidine nucleotide

precursors by inhibiting their synthesis or by competing with them in DNA or RNA
synthesis.
Pharmacological action
Cytotoxic action
Predominant on bone marrow
Immunosuppressive action
Anti inflammatory action
Prevents clonal expansion of B &T lymphocytes
Interfere with release of inflammatory cytokines IL-2,IL-6,IL-8 and TNF
Decrease rheumatoid factor production
ADR
Megaloblastic anaemia
Thrombocytopenia
Leukopenia
Aplasia,
Oral, intestinal ulcer
Diarrhoea
Alopecia
Liver damage
Nephropathay
Substance essential for the synthesis of the nucleic acid bases-methotrexate
Substance which in corporated into nucleic acid chain purine and pyramidine antagonist
FOLATE ANTAGONIST-Methotrxate, Pemetrexed
1.METHOTREXATE
Methotrexate is the most widely used antimetabolite in cancer chemotherapy .
It mainly acts by inhibiting the enzyme dihydro folate reductase(DHFR),which is essential
in synthesis of folate.
It is cell cycle specific and kills cells in S phase.
It mainly inhibits the synthesis of DNA also affects RNA and protein synthesis
MECHANISM OF ACTION – Methotrexate structurally resembles follic acid
1.folic acid is essential for the production of co enzyme,tetrahydrofolic acid(THF).
2. The conversion of folate to THF is carried out by an enzyme,folate reductase.
3. Methotrexate competes with folic acid for this enzyme by binding irreversibly to folate
reductase,thus inhibiting the production of THF.
4. lack of the co enzyme THF leads to inhibition of DNA synthesis and consequently of
cell replication
 Dihydro folate reductase
• Dihydrofolic acid __ Tetrahydrofolic acid
(DHFA) (THFA)

Methotrexate

Purines and thymidylate

DNA
• Pharmacological actions
• Cytotoxic actions
Predominant on bone marrow
Ulceration of intestinal mucosa
Crosses placenta interferes with embroyogenesis foetal malformations and
death
• Immunosupressive action
Prevents clonal expansion of B & T lymphocytes
• Anti-Inflammatory action
Interferes with release of inflammatory cytokines IL-2, IL-6,IL-8 & TNFalpha
↓ Rheumatoid Factor production
• Uses of methotrexate
• Antineoplastic
Choriocarcinoma and tropoblast tumor
Remission of ALL in children
Carcinoma on breast, head & neck, bladder, ovarian cancer
• Immuno-supressive agent
Rheumatoid arthritis, resistant asthma
Crohns disease, wegeners granulomatosis
Prevention of graft versus host reaction
• Psoriasis
• Medical termination of pregnancy
• Non –Hodgin lymphoma
Adverse effects
• Megaloblastic anemia
•Thrombocytopenia, leukopenia, aplasia
• Oral, intestinal ulcer , diarrhoea
• Alopecia , liver damage, nephrpathy
Treatment of methotrexate toxicity
Folinic acid (citrovorum factor, N5 Formyl THF)
IM/IV 8 to 24 hrs after initiation of methotrexate
120 mg in divided doses in first 24 hrs, then 25 mg oral/IM 6 hrly for next 48 hrs
• Mechanism of Resistance
 Impaired transport of methotrexate into cells
 Production of altered forms of DHFR that have decreased affinity for the inhibitor
 Increased concentration of intracellular DHFR through gene amplification or altered
gene regulation
 Decreased ability to synthesize methotrexate polyglutamates
 Increased drug efflux
• PURINE ANTAGONISTS : 6- mercaptopurine , 6 Thioguanine(6TG)
MERCAPTOPURINE
6-Mercaptopurine is an analogue of purine and is highly effective anticancer drug
Acts in S phase of cell
MOA
The drug is converted in the cells to ribonucleotide of 6-mercaptopurine,which then suppresses
the denovo biosynthesis of purines and hence of DNA.
• Use: Acute Lymphoblasticleukemia (ALL)
Choriocarcinoma, Used in solid tumour
ADR
– Bone marrow & GIT mainly
Hepatic necrosis rarely
– Hyperuricaemia
PYRAMIDINE ANTAGONISTS- 5-FU ( fluorouracil),Cytarabine

It must be converted in the body to the corresponding deoxynucleotide(5-fluoro-

2-deoxy uridine monophosphate),which inhibits thymidylate synthesis and
blocks the conversion of deoxyuridilic acid to deoxythymidilic acid.
The result is inhibition of DNA synthesis but not RNA
• USE
• Used for many solid tumour
• Colon,
• rectum,
• stomach,
• Pancreas,
• Liver, Urinary bladder,
• Head and Neck
• ADR
Myelosuppression
Mucosititis
Diarrhoea
Nausea and Vomiting
Peripheral neuropathy (Hand-Foot syndrome)
• NATURAL PRODUCTS- Vinca alkaloids , Taxanes, Epipodophyllotoxins ,
Camptothecins,Antibiotics, Echinocandins, Anthracenedione , Enzyme
Vinca alkaloids
• Obtained from periwinkle plant ( Vinca Rosea)
• Vincristine, vinblastine, vindesine, vinorelbine

Vinblastine and vincristine

Bind to beta tubulin(drug –tubulin complex)
Disruption of mitotic spindle
Chromosome fail to move apart during mitosis
Metaphase arrest
Cell division is inhibited
Hence,they are both cycle specific and phase-
specific.
VINCRISTINE VINBLASTINE
USE: USE
Childhood acute lymphoblastic leukaemia
Acute myeloid leukaemia Employed with other drugs for Hodgkin disease,
Hodgkin,s disease Kaposi sarcoma
Wilm,s tumour Neuroblastoma
Ewing,s sarcoma Non –Hodgkin,s lymphoma
Neuroblastoma Breast and testicular carcinoma
Carcinoma of lungs
ADR ADR
Peripheral neuropathy
Alopecia Bone marrow depression
Ataxia SIADH
Nerve palsies
Autonomic dysfunction (Postural hypotension
,Paralytic ileus, Urinary retention,)
Seizures
Inappropriate secretion of ADH(SIADH)
Taxanes - Paclitaxel & docetaxel
• Plant product obtained from bark of Pacific Yew ( Taxus Brevifolia) & European Yew (Taxus
Buccata)

Paclitaxel bind to beta tubulin

Stabilizes polymerized tubulin
Formation of abnormal microtubles (spindle poison)
Inhibits mitosis
PACLITAXEL DOCETAXEL
Administered IV Oral

USES USES
Metastatic Ovarian and Breast carcinoma
Head and Neck cancer Ovarian Cancer
Small cell Lung cancer Breast canncer
Esophageal adenocarcinoma Small cell cancer lung,pancreatic,gastric and
Urinary and hormone refractory Prostate cancer head , neck carcinoma
AIDS related kaposi,s sarcoma Neutropenia
ADR Arrhythmias
Anaphylactoid reaction because of solvent Fall in BP
cremophor
Reversible myelosuppression( Granulocytopenia)
Stocking and glove neuropathy
Nausea
Chest pain
Arthalgia
Myalgia
ANTICANCER ANTIBIOTICS-Actinomycin D ,Doxorubucin
,Bleomycin,Mitomycin ,Daunorubicin ,Epirubucin
ACTINOMYCIN D
• Actinomycin D is very potent antineoplastic antibiotic obtained from the species of
STREPTOMYCES.
MECHANISM OF ACTION
The drug intercalates into the minor groove of double helix between guanine-
cytosine base pairs of DNA and interfere with the movement of RNA polymerase
along the gene and thus preventing transcription.
It may also cause strand breaks and stabilize DNAtopoisomerase II complex
. CLINICAL USES
It is used in the combination with surgery and vincristine for the treatment of wilm’s
tumour and soft tissue sarcomas.
• ADVERSE EFFECT
• Vomiting
• Stomatitis
• Diarrhoea
• Bone marrow depression.
• It can damage the skin that is exposed to radiation
2. DACTINOMYCIN
Uses:
• Wilms tumor,
• gestational choriocarcinoma
• Adverse effects
• bone marrow supression
• Irritant like meclorethamine
• sensitizes to radiation, and inflammation at sites of prior radiation therapy may
occur
• Gastrointestinal adverse effects
• ENZYMES- L-asparaginase
Isolated from E.coli Use: Acute Lymphocytic Leukemia (ALL)
Adverse Effect• Hepatic damage
• Hypersensitivity , hemorrhage
• Hyperglycemia, headache, hallucinations , confusion, coma
• HYDROXY UREA
Ribonucleoside diphosphate
reductase Adverse Effects: Myleosuppression
Ribonucleotides - Deoxyribonucleotides Hypersensitivity

Hydroxy urea Hyperglycemia

• Uses: CML, Polycythemia, psoriasis Hypoalbuminea