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FINALS
PRINCIPLES OF
CANCER TREATMENT
1. True of cancer growth:
a. Cancer is very different from a normal organ attempting to
regulate its own growth. FALSE. IT CAN MIMICS AN ORGAN.
b. Cancers have set an appropriate limit on how much growth
should be permitted. FALSE. IT HAS NOT SET AN APPROPRIATE
LIMIT ON HOW MUCH GROWTH SHOULD BE PERMITTED
c. Cancer cells that are not dividing are heterogeneous. TRUE.
d. Some cancer cells have not sustained too much genetic damage
to replicate but have defects in their death pathways that permit
their survival. FALSE. SOME CANCER CELLS HAVE SUSTAINED TOO
MUCH GENETIC DAMAGE.
Cancer growth
cancer mimics an organ attempting to regulate its
own growth
cancers have not set an appropriate limit on how
much growth should be permitted
Some have sustained too much genetic damage to
replicate but have defects in their death pathways
that permit their survival
NORMAL ORGANS & CANCERS
(1) a population of cells in cycle and actively renewing
(2) a population of cells not in cycle
cells that are not dividing are
heterogeneous
some have sustained too much genetic
damage to replicate but have defects in
their death pathways that permit their
survival
c. Efforts to treat the tumor and reduce its size can result in an
increase in the growth fraction and an increase in growth
rate . TRUE.
ANSWER: C
Tumors follow a Gompertzian
growth curve, with the apparent
growth fraction of a neoplasm
being high with small tumor
burdens and declining until, at
the time of diagnosis, with a
tumor burden of 15 109
tumor cells [kills the patient at a
tumor cell burden of about 1012
(1 kg)], the growth fraction is
usually 14% for many solid
tumors. By this view, the most
rapid growth rate occurs before
the tumor is detectable.
Specific cellular mechanisms promote entry or withdrawal
of tumor cells from the cell cycle. For example, when a
tumor recurs after surgery or chemotherapy, frequently its
growth is accelerated and the growth fraction of the tumor
is increased. This pattern is similar to that seen in
regenerating organs.
Partial resection of the liver results in the recruitment of
cells into the cell cycle, and the resected liver volume is
replaced. Similarly, chemotherapy-damaged bone marrow
increases its growth to replace cells killed by chemotherapy.
However, cancers do not recognize a limit on their
expansion.
3. True of Gompertzian tumor
growth:
a. the growth fraction of a tumor increases exponentially over time.
FALSE. IT DECLINES EXPONENTIALLY W/ TIME
b. the growth rate of a tumor peaks before it is clinically detectable.
TRUE
c. tumor size increases dramatically then slows down as the tumor
reaches the size at which limitation of nutrients or auto or host
regulatory influences can occur. FALSE. TUMOR SIZE INCREASES
SLOWLY NOT DRAMATICALLY.
d. tumor becomes detectable at a burden of about 10^3 cells and kills
the patient at a tumor cell burden of about 10^43. FALSE. IT IS
DETECTABLE AT 10^9, & KILL THE PATIENT AT 10^12(1KG)
Gompertzian tumor growth:
Growth fraction Tumor size
starts at 100% with the increases slowly
first transformed cell goes through an exponential phase
declines exponentially slows again as the tumor reaches the size at
over time until at the time which limitation of nutrients or auto- or host
of diagnosis regulatory influences can occur
ANSWER: TRUE
IT FOLLOWS A
GOMPERTZIAN GROWTH
CURVE
4. TRUE OR FALSE. Peak growth rate of the
tumor happens once tumor is clinically
detectable.
ANSWER: FALSE-
The most rapid growth rate occurs before the tumor is detectable. An
alternative explanation for such growth properties may also emerge
from the ability of tumors at meta- static sites to recruit circulating
tumor cells from the primary tumor or other metastases. An additional
key feature of a successful tumor is the ability to stimulate the
development of a new supporting stroma through angiogenesis and
production of proteases to allow invasion through basement membranes
and normal tissue barriers. The maximum growth rate occurs at 1/e,
the point at which the tumor is about 37% of its maximum size
(marked with an X in the graph).
5. True of Gompertzian tumor
growth:
a. The growth of a tumor increases exponentially over time
FALSE. IT DECLINES EXPONENTIALLY OVER TIME
a. The growth rate of a tumor peaks before it is clinically detectable
b. Tumor size increases dramatically then slows down as the tumor
reaches the size at which initiation of nutrients or auto or host
regulatory influences can occur.
FALSE. TUMOR SIZE INCREASES SLOWLY NOT DRAMATICALLY
c. Tumor becomes detectable at a burden of about 103cells and kills the
patient at a tumor cell burden of about 1012.
FALSE. TUMOR BECOMES DETECTABLE AT A BURDEN OF ABOUT
109CELLS NOT 103CELLS
Gompertzian growth curve
The growth fraction of a tumor declines exponentially over time
The growth rate of a tumor peaks before it is clinically
detectable
Tumor size increases slowly, goes through an exponential phase,
and slows again as the tumor reaches the size at which limitation
of nutrients or auto- or host regulatory influences can occur.
The maximum growth rate occurs at 1/e, the point at which the
tumor is about 37% of its maximum size (marked with an X).
DETECTABLE KILL
10^9 (1 cm3) cells 10^12 (1 kg).
GOAL OF CANCER TREATMENT
PRIMARY: ERADICATE CANCER
IF NOT MET: SHIFT TO PALLIATION
AMELIORATION OF SYMPTOMS
PRESERVATION OF QUALITY OF LIFE(MOST IMPORTANT)
WHEN CURE OF CA IS POSSIBLE, CANCER TREATMENTS MAY
BE UNDERTAKEN DESPITE THE CERTAINTY OF SEVERE AND
LIFE THREATENING TOXICITIES
GUIDING PRINCIPLE
PRIMUM SUCCERRERE
FIRST HASTEN TO HELP
A. Surgery
B. Radiation therapy
C. Biologic therapy
D. Brachytherapy
FOUR MAIN TYPES OF CANCER
TREAMENT
LOCAL SYSTEMIC
*EFFECTS CAN INFLUENCE THE
BEHAVIOR OF TUMOR AT
REMOTE SITES
1. SURGERY 3. CHEMOTHERAPY- INCLUDES
HORMONAL AND MOLECULAR
TARGETED THERAPY
2. RADIATION THERAPY- 4. BIOLOGIC THERAPY- INCLUDES
INCLUDES PHOTODYNAMIC IMMUNOTHERAPY & GENE
THERAPY
KEY FEATURE OF SUCCESSFUL
TUMOR
ability to stimulate the development of a new
supporting stroma through:
Angiogenesis
Production of proteases
to allow invasion through basement membranes
and normal tissue barriers
Specific cellular mechanisms promote
entry or withdrawal of tumor cells from
the cell cycle.
E.g. when a tumor recurs after surgery or chemotherapy,
frequently its growth is accelerated and the growth fraction of
the tumor is increased.
Chemotherapy-damaged bone marrow increases its growth
to replicated cells killed by chemotherapy.
This pattern is similar to that seen in regenerating organs.
Partial resection of the liver results in the recruitment of cells
into the cell cycle.
PRINCIPLES OF
CANCER SURGERY
CANCER PREVENTION
7. Surgery is used in cancer prevention of
pre- malignant lesion in:
A. Breast
B. Colon- also includes skin & cervix
C. Ovary
D. Lung
Also can be prevented in people who
have:
1. An underlying disease Colectomy in those with pancolonic
involvement with ulcerative colitis
2. The presence of Colectomy for familial polyposis
genetic lesions Thyroidectomy for multiple endocrine
neoplasm type 2
Bilateral mastectomy or oophorectomy for
familial breast or ovarian cancer syndrome
3. The presence of a Orchiectomy
developmental anomaly - with an undescended testis
8. Surgical procedure that has systemic
antitumor effect on some malignancy:
A. Colectomy
B. Orchiectomy- also includes oophorectomy
& adrenalectomy
C. Mastectomy
D. Cholecystectomy
9. True of use of Surgery as
prophylaxis.
a. Colectomy for multiple endocrine neoplasia type 2 . FALSE.
COLECTOMY IS FOR THOSE W/ PANCOLONIC ULCERATIVE COLITIS
WHILE MEN2 IS AN INDICATION FOR THYROIDECTOMY.
b. Hysterectomy for familial breast or ovarian cancer syndromes.
FALSE. IT IS OOPHORECTOMY NOT HYSTERECTOMY FOR FAMILIAL
BREAST OR OVARIAN CANCER SYNDROMES.
c. Orchiectomy in those with prostate cancer. FALSE. IT IS FOR
THOSE W/ UNDESCENDED TESTIS.
d. in some cases, prophylactic surgery is more radical than the
surgical procedures used to treat the cancer after it develops
Cancer Prevention/ Prophylaxis
Those who are at Prevention/Prophylaxis
risk of cancer from
either
an underlying disease Colectomy Pancolonic involvement w/
ulcerative colitis
the presence of genetic Colectomy familial polyposis
lesions thyroidectomy MEN type 2
bilateral familial breast or
mastectomy or ovarian cancer syndromes
oophorectomy
the presence of a orchiectomy w/an undescended testis
developmental anomaly
Surgery can also be associated with systemic
antitumor effects in the setting of hormonally
responsive tumors.
Oophorectomy and/or adrenalectomy
May eliminate estrogen Hormones that drive certain
production breast cancer
Orchiectomy
May reduce androgen Hormones that drive all
production prostate cancers
In patients with colon cancer who have fewer than five liver
metastases restricted to one lobe and no extrahepatic
metastases, hepatic lobectomy may produce long-term disease-
free survival in 25% of selected patients.
21. TRUE OR FALSE. Surgery is the first
treatment modality of choice in Stage III
Breast cancer.
Rationale:
Answer False
In some settingse.g., bulky testicular cancer or stage III
breast cancersurgery is not the first treatment modality
PALLIATION
22. Surgery as palliation can be
applied to the following cause/s:
a) Limb-sparing surgery followed by adjuvant
radiation in therapy and chemotherapy for
osteosarcoma. a form of treatment
b) Axillary lymph dissection in breast cancer. a form
of treatment
c) Inferior vena cava filter for recurrent pulmonary
emboli . a form of palliation
Surgery is used in a number of ways for palliative or supportive care
of the cancer patient, not related to the goal of curing the cancer.
These include insertion and care of central venous catheters, control
of pleural and pericardial effusions and ascites, caval interruption for
recurrent pulmonary emboli, stabilization of cancer-weakened
weight- bearing bones, and control of hemorrhage, among others.
Surgical bypass of gastrointestinal, urinary tract, or biliary tree
obstruction can alleviate symptoms and prolong survival. Surgical
procedures may provide relief of otherwise intractable pain or reverse
neurologic dysfunction (cord decompression).
Splenectomy may relieve symptoms and reverse hypersplenism.
Intrathecal or intrahepatic therapy relies on surgical placement of
appropriate infusion portals.
23. Surgery employed as supportive
care (palliation) except:
a. insertion of central venous catheters. PALLIATION
b. control of pleural and pericardial effusions and
ascites, caval interruption for recurrent pulmonary
emboli. PALLIATION
c. Stabilization of cancer weakened weight -bearing
bones. PALLIATION
d. Modified radical mastectomy for breast cancer
stage 2. TREATMENT
Palliation
Insertion of central -control of pleural and pericardial
venous catheters effusions and ascites
Caval interruption -for recurrent pulmonary emboli
Stabilization -cancer-weakened weight-bearing
bones
Surgical bypass of GIT, -alleviate symptoms
urinary tract, or biliary -prolong survival
tree obstruction
Palliation
Cord decompression -relief of otherwise intractable pain
-reverse neurologic dysfunction
Splenectomy -relieve symptoms
reverse hypersplenism
Surgical placement of -Used in intrathecal or intrahepatic
appropriate infusion therapy
portals
Correct other -Such as adhesions or strictures
treatment related
toxicities
24. TRUE OR FALSE. In patients with colon
cancer who have fewer than five liver
metastases restricted to one lobe and no
extrahepatic metastases, hepatic lobectomy
(metastectomy) may produce longterm disease-
free survival in 25% of selected patients.
Answer true
PRINCIPLES OF
RADIATION THERAPY
25. Which of the following statements
regarding radiation therapy is/are
correct?
a. Radiation is a physical form of treatment that
damages any tissue in its path
b. Radiation causes breaks in DNA and generates free
radicals from cell water that may damage cell
membranes, proteins and organelles.
c. Radiation damage is augmented dependent on only
oxygen, hypoxemic cells are more resistant
d. all of the above
26. Radiation:
A. Damage cause is dependent on the formation of radicals.
FALSE. DAMAGE IS DEPENDENT ON OXYGEN
B. Its selectivity for cancer cells may be due to defects in cancer
cells ability in repair defective RNA and other damage. FALSE. IT
IS REPAIR OF DEFECTIVE DNA NOT RNA.
C. A physical form of treatment that damages any tissue in its
path. TRUE.
D. Its selectivity for cancer cells may be due to defects in host
cells ability to repair sublethal RNA and other damage. FALSE. IT
IS THE CANCER CELLS ABILITY TO REPAIR, BUT NOT OF THE
HOST.
PHYSICAL PROPERTIES AND
BIOLOGIC EFFECTS
Exposure to ionizing radiation Radiation is a physical form
is constant of treatment that damages
Sources of radiation any tissue in its path
- The sun and other cosmic Selectivity for cancer cells
sources may be due to defects in a
- The ground cancer cells ability to repair
- The air we breathe sublethal DNA and other
- The food we ingest damage
- From within our bodies
PHYSICAL PROPERTIES AND
BIOLOGIC EFFECTS
Radiation causes breaks in Augmentation of oxygen
DNA and generates free presence is one basis for
radicals from cell water that radiation sensitization
may damage cell membranes, Sulfhydryl compounds
proteins, and organelles interfere with free radical
Radiation damage is generation and may act as
augmented dependent on radiation protectors.
oxygen Most radiation-induced cell
Hypoxemic cells are more damage is due to the
resistant formation of hydroxyl radicals
PHYSICAL PROPERTIES AND
BIOLOGIC EFFECTS
The dose-response curve for cells have both linear and
exponential components
Linear component From double-stranded DNA
breaks produced by single hit
A. Bone
B. Heart
C. Skeletal muscle
D. Nerve
Principles of radiation therapy
Most sensitive Sensitive Resistant
Male testis Hematopoietic Heart
Female ovary system Skeletal muscle
Bone marrow Mucosal lining of Nerves
the intestinal tract
Any bone marrow in Organs with less
a radiation field will Organs with more need for cell renewal
be eradicated by self-renewal as a *Bone is among the
therapeutic part of normal most radioresistant
irradiation. homeostasis organ
30. Acute toxicity of radiation:
A. Radiation enteritis
B. Mucositis
C. Dental caries
D. Thyroid failure
Acute toxicities
Often these can be alleviated by interruption of treatment:
Mucositis
Skin erythema (ulceration in severe cases)
Bone marrow toxicity
a. Radiation enteritis
b. Mucositis
c. skin erythema/ulceration
d. bone marrow toxicity
Acute toxicities Chronic toxicities
Mucositis are more serious
skin erythema Radiation of the head and neck region thyroid
(ulceration in severe cases) failure.
bone marrow toxicity Cataracts and retinal damage blindness.
Salivary glands stop making saliva dental caries
and poor dentition
Taste and smell can be affected
Mediastinal irradiation 3-fold risk of fatal MI
Often these can be Other late vascular effects
alleviated by interruption of chronic constrictive pericarditis
treatment. lung fibrosis
viscus stricture
spinal cord transection
radiation enteritis
40. Most radiation sensitive organs,
except:
a. testis
b. bone
c. bone marrow
d. ovaries
PRINCIPLES OF RADIATION THERAPY
Most sensitive 1. male testis
organs 2. female ovary
3. bone marrow
Any bone marrow in a radiation field will be
eradicated by therapeutic irradiation
Sensitive Organs with more self-renewal
as a part of normal homeostasis
1. hematopoietic system
2. mucosal lining of the intestinal tract
Resistant to Organs with less need for cell renewal
radiation effects 1. Heart
2. Skeletal muscle
3. Nerves
41. TRUE OR FALSE.Most radiation-induced cell
damage is due to the formation of hydroxyl radicals.
ANSWER- TRUE
Therapeutic radiation is ionizing; it damages any tissue in its
path.
The selectivity of radiation for caus- ing cancer cell death may be
due to defects in a cancer cells ability to repair sublethal DNA
and other damage.
Ionizing radiation causes breaks in DNA and generates free
radicals from cell water that may damage cell membranes,
proteins, and organelles.
Radiation damage is augmented by oxygen; hypoxic cells are
more resistant.
Augmentation of oxygen presence is one basis for radiation
sensitization. Sulfhydryl compounds interfere with free radical
generation and may act as radiation protectors.
Most radiation-induced cell damage is due to the formation
of hydroxyl radicals from tissue water:
Ionizingradiation+H2OH2O+ +e
H2O+ + H2O H3O+ + OH
OH cell damage
42. TRUE OR FALSE. Radiation is
quantitated based on the amount of
radiation generated by the machine.
ANSWER: FALSE- Radiation is quantitated based on
the amount of radiation absorbed by the tumor in
the patient; it is not based on the amount of radiation
generated by the machine. Radiation dosage is defined
by the energy absorbed per mass of tissue. Radiation
dose is measured by placing detectors at the body
surface or based on radiating phantoms that resemble
human form and substance, containing internal
detectors.
43. TRUE OR FALSE. Cisplatin and Hydroxyurea
are both radiosensitizing agents.
TRUE- Certain drugs used in cancer treatment may
also act as radiation sensitizers. For example,
compounds that incorporate into DNA and alter its
stereochemistry (e.g., halogenated pyrimidines,
cisplatin) augment radiation effects at local sites, as
does hydroxyurea, another DNA synthesis inhibitor.
These are important adjuncts to the local treatment of
certain tumors, such as squamous head and neck,
uterine cervix, and rectal cancers.
44. TRUE OR FALSE. Brachytherapy can be
used to treat cervical and prostate
cancers.
TRUE- Brachytherapy involves placing a sealed source of
radiation into or adjacent to the tumor and withdrawing the
radiation source after a period of time. Advantage: used to
treat prostate and cervical cancer
Disadvantage: short range of radiation effects (the inverse
square law); the inability to shape the radiation to fit the
target volume.
Adverse effects due to toxic exposure to the radiation of
normal tissue: concomitant radiation enteritis or cystitis in
cervix cancer; brain injury in brain tumors.
45. Brachytherapy can be used to
treat cervical and prostate cancers.
Rationale:
Answer - true
54. TRUE OR FALSE. Radiation is
quantified based on the amount of
radiation generated by the machine
Rationale:
Answer - false
Radiation is quantitated on the basis of the amount of
radiation absorbed in the patient; it is not based on the
amount of radiation generated by the machine.
Harrisons Principles of Internal Medicine 18th edition
PRINCIPLES OF
CHEMOTHERAPY
ENDPOINTS OF DRUG ACTION
1. The existence of compounds that would be magic bullets
that might bind to tumors, owing to the affinity of the agent for
the tumor Paul Ehrich
2. Observed toxic effects of certain mustard gas derivatives on
the bone marrow during World War I lead to the idea that
smaller doses of these agents might be used to treat tumors of
marrow-derived cells
3. Certain tumors from hormone-responsive tissues, e.g. breast
tumors, could shrink after oophorectomy-->endogenous
substances promoting the growth of a tumor might be
antagonized
55. Advanced cancer with possible
cure with chemotherapy:
A. Small cell lung CA
B. Breast CA
C. Melanoma
D. Bladder CA
56. Advanced cancers with possible
cure, except:
a. Hodgkin's disease
b. Seminoma
c. Ewing's sarcoma
d. Pancreatic carcinoma
Advanced Cancers with Possible Cure
Acute lymphoid and acute myeloid Pediatric neoplasms
leukemia (pediatric/ adult) Wilms tumor
Germ cell neoplasms Embryonal rhabdomyosarcoma
Embryonal carcinoma Ewings sarcoma
Teratocarcinoma Peripheral neuroepithelioma
Seminoma or dysgerminoma Neuroblastoma
Choriocarcinoma Ovarian carcinoma
Hodgkins disease (pediatric/ Non-small-cell lung carcinoma
adult) (stage III)
Squamous carcinoma (anus) Lymphomascertain types
(pediatric/adult)
Gestational trophoblastic
neoplasia
Small-cell lung carcinoma
57. Cancers possibly cured with chemotherapy
as adjuvant to surgery, EXCEPT:
a. Breast carcinoma
b. Hepatocellular carcinoma
c. Colorectal carcinoma
d. Osteogenic sarcoma
CANCERS POSSIBLY CURED WITH CHEMOTHERAPY AS ADJUVANT TO
SURGERY (BCROS)
BREAST CARCINOMA OSTEOGENIC SARCOMA
COLORECTAL CARCINOMA SOFT TISSUE SARCOMA
3. HORMONAL THERAPIES
The 1st form of targeted therapy
Capitalize on the biochemical pathways underlying estrogen & androgen
function & action
2. TARGETED AGENTS
Refer to small molecules or biologicals
- Generally macromolecules such as antibodies or cytokines
Designed & developed to interact with a defined molecular target
- Important in either maintaining the malignant state, or
- selectively expressed by the tumor cells
Targeted therapies seek to capitalize on the biology behind the aberrant
cellular behavior as a basis for therapeutic effects
4. BIOLOGIC THERAPIES
Are often macromolecules that have a particular target
e.g., antigrowth factor or cytokine antibodies
May have the capacity to regulate growth of tumor cells
Induce a host immune response to kill tumor cells
Include not only antibodies but cytokines & gene therapies
CONVENTIONAL
CHEMOTHERAPY
A. DIRECT DNA-INTERACTIVE
AGENTS- ALKYLATING
ANTI-TUMOR ANTIBIOTICS OF
ALKYLATING AGENTS TOPOISOMERASE POISONS
CYCLOPHOSPHAMIDE DOXORUBICIN
FOSFOMIDE DAUNORUBICIN
NITROGEN MUSTARD
IDARUBICIN
CHLORAMBUCIL
MALPHALAN BLEOMYCIN
PROCARBAZINE MITOXANTRONE
DACARBAZINE ETOPOSIDE
TEMOZOLAMIDE CAMPTOTHECIN
CISPLATIN
TOPOTECAN
CARBOPLATIN
OXALIPLATIN CPT-11/IRINOTECAN
67. True of alkalyting agents
A. Stabilizes microtubules preventing cell division
B. May cause second neoplasm
C. Cell cycle specific agents
ALKYLATING AGENTS
Alkylating agents as a class are cell cycle phasenonspecific agents.
They break down, either spontaneously or after normal organ or tumor
cell metabolism, to reactive intermediates that covalently modify bases
in DNA.
This leads to cross-linkage of DNA strands or the appearance of breaks
in DNA as a result of repair efforts.
Broken or cross-linked DNA is intrinsically unable to complete
normal replication or cell division; in addition, it is a potent activator of
cell cycle checkpoints and further activates cell-signaling pathways that
can precipitate apoptosis.
As a class, alkylating agents
share similar toxicities:
myelosuppression, alopecia,
gonadal dysfunction,
mucositis, and pulmonary
fibrosis.They differ greatly in
a spectrum of normal organ
toxicities.
As a class, they share the
capacity to cause second
neoplasms, particularly
leukemia, many years after
use, particularly when used
in low doses for protracted
periods.
68. Cyclophosphamide is inactive unless
metabolized by the liver to 4-
hydroxycyclophosphamide which decomposes
into an alkylating species as well as to this
chemical which causes chemical cystitis
a) Chlorocetaldehyde
b) Ifosfamide
c) 2-mercaptoethanesulfonate
d) Acrolein
CYCLOPHOSPHAMIDE
An inactive drug unless
metabolized by the liver to
4-hydroxy-cyclophosphamide,
which decomposes into an
alkylating species, as well
as to chloroacetaldehyde
and acrolein. The latter
causes chemical cystitis;
therefore, excellent
hydration must be
maintained while using
cyclophosphamide
69. Toxicity of doxorubicin
a) Causes chronic cardiotoxicity in the form of atrial and
ventricular dysrhythmias.
FALSE. IT IS ACUTE CARDIOTOXICITY.
a) Cardiotoxicity has been related to topoisomerase action.
FALSE. It is related to iron-catalyzed oxidation and reduction of
doxorubicin not to topoisomerase action.
a) Doxorubicins cardiotoxicity is increased when given together
with trastuzumab (Herceptin), the anti-HER2/neu antibody.
TRUE
b) Powerful vesicant with no known antidote to extravasation.
FALSE. IT HAS A KNOWN ANTIDOTE- Dexrazoxane
70. Cardiotoxicity of Doxuribicin is related to:
A. Topoisomerase II action
*related to iron catalyzed oxidation and reduction
a. Stomatitis
b. Bone marrow suppression
c. CNS Dysfunction
d. Pulmonary Embolism
5FU
Oral bioavailability varies unreliably, but orally administered analogues
of 5FU such as capecitabine have been developed that allow at least
equivalent activity to many parenteral 5FU-based approaches.
Intravenous administration of 5FU leads to
bone marrow suppression after short infusions
stomatitis after prolonged infusions.
Leucovorin augments the activity of 5FU by promoting formation of the
ternary covalent complex of 5FU, the reduced folate, and TS.
Less frequent toxicities include CNS dysfunction, with prominent
cerebellar signs, and endothelial toxicity manifested by thrombosis,
including pulmonary embolus and myocardial infarction.
C. MITOTIC SPINDLE INHIBITORS
VINCA ALKALOIDS TAXANES
VINCRISTINE DOCETAXEL
VINBLASTINE PACLITAXEL
78. True of mitotic spindle inhibitors
a) Docetaxel binds to tubulin dimer with the result that
microtubules are disaggregated resulting to block of
growing cells in M-phase. FALSE. IT IS VINCRISTINE THAT
BINDS TO TUBULIN DIMER NOT DOCETAXEL.
b) Vincristine is a powerful vesicant, and infiltration can be
treated by cold compress. FALSE. IT IS TREATED W/ LOCAL
HEAT NIT COLD COMPRESS
c) The taxanes stabilize microtubules against
depolymerisation.
ANSWER: C
Vincristine (not docetaxel) binds to the tubulin dimer with the result that
microtubules are disaggregated. This results in the block of growing cells in
M-phase; however, toxic effects in G1 and S-phase are also evident,
Vincristine is metabolized by the liver, and dose adjustment in the presence
of hepatic dysfunction is required. It is a powerful vesicant, and infiltration
can be treated by local heat and infiltration of hyaluronidase.
The taxanes include paclitaxel and docetaxel. These agents differ from the
vinca alkaloids in that the taxanes stabilize microtubules against
depolymerization. The stabilized microtubules function abnormally and
are not able to undergo the normal dynamic changes of microtubule
structure and function necessary for cell cycle completion.
VINCRISTINE VINBLASTINE
MOA:
1. Binds to the tubulin dimer with the result that microtubules are disaggregated
2. Block of growing cells in M-phase
(toxic effects in G1 & S-phase are also evident)
KINETICS
- Metabolized by the liver
o Dose adjustment in hepatic dysfunction is required
ADMIN
- Powerful vesicant
o Infiltration can be treated by local heat & infiltration of hyaluronidase
Clinically used IV doses neurotoxicity in the MORE myelotoxic with more frequent
form of glove-and-stocking neuropathy is thrombocytopenia
frequent - MORE mucositis & stomatitis
- Acute neuropathic effects include jaw pain,
paralytic ileus, urinary retention, & the
syndrome of inappropriate antidiuretic hormone
secretion
- Myelosuppression is NOT seen
79. True of mitotic spindle inhibitors:
a. Vinca alkaloids like vincristine stabilizes microtubules against depolymerization.
FALSE. IT IS TAXANES THAT STABILIZES MICROTUBULES AGAINST
DEPOLYMERISATION.
b. Premedication with dexamethasone and diphenhydramine and cimetidine
completely eliminate the risk of hypersensitivity reactions to the paclitaxel
vehicle.
FALSE. PREMEDICATION IS DECREASES THE RISK BUT NOT ELIMINATE.
c. Paclitaxel may cause hypersensitivity reactions, myelosuppression,
neurotoxicity in the form of glove-and-stocking numbness and paresthesia
d. Cardiac rhythm disturbances were observed in phase I and II trials of taxanes,
most common of which is symptomatic bradycardia.
FALSE. IT IS ASYMPTOMATIC BRADYCARDIA
HORMONAL THERAPY
ESTROGEN PROGESTATIO AROMATASE ANDROGEN TESTICULAR
RECEPTOR NAL AGENTS INHIBIOTRS DEPRIVATION ANDROGEN
ANTAGONIST SUPRESSION
TAMOXIFEN MPA IRREVERSIBLE DIETHYLSTILBE LEUPROLIDE
ANDROGENS( -EXEMESTANE STROL GOSERELIN
HALOTESTIN) REVERSIBLE
ESTROGENS -
ANASTROZOLE
-LETROZOLE
80. Aromatase Inhibitors:
a. family of enzymes that catalyze the formation of estrogen
exclusively in the ovaries
b. are of two types, the irreversible steroid analogues such as
anastrozole and the reversible inhibitors such as exemestane
c. superior to tamoxifen n the adjuvant treatment of breast
cancer in postmenopausal patients with estrogen receptor-
positive tumors
d. protective against osteoporosis
Answer: C
Aromatase refers to a family of enzymes that catalyze the formation of
estrogen in various tissues, including the ovary and peripheral adipose
tissue and some tumor cells.
Aromatase inhibitors are of two types, the irreversible steroid analogues
such as exemestane and the reversible inhibitors such as anastrozole or
letrozole.
Anastrozole is superior to tamoxifen in the adjuvant treatment of breast
cancer in postmenopausal patients with estrogen receptorpositive
tumors.
Letrozole treatment affords benefit following tamoxifen treatment.
Adverse effects of aromatase inhibitors may include an increased risk of
osteoporosis.
TARGETED THERAPY
Diagnostically Guided Protein Multikinase Proteasome Histone mTOR Inhibitors
Kinase Antagonists inhibitors Inhibitors Deacetylase
Inhibitors
IMATINIB ERLOTINIB SORAFINIB BORTEZOMIB VORINOSTAT TEMSIROLIMUS
NILOTINIB AFATINIB &SUNITINIB CARFILZOMIB ROMIDEPSIN EVEROLIMUS
DASATINIB CRIZOTINIB PAZOPANIB
BOSUTINIB VEMURAFENIB REGORAFENIB
PONATINIB DABRAFENIB VANDETANIB
GEFITINIB TRAMETINIB CABOZANTINIB
AXITINIB
G1
first phase
preparations are made to replicate the genetic material
The cell stops before entering the DNA synthesis phase, or S phase, to take
inventory
Are we ready to replicate our DNA?
Is the DNA repair machinery in place to fix any mutations that are detected?
Are the DNA replicating enzymes available?
Is there an adequate supply of nucleotides?
Is there sufficient energy?
Cell cycle checkpoints
Retinoblastoma protein, Rb
-main brake on the process is the retinoblastoma protein, Rb
When the cell determines that it is prepared to move ahead,
sequential activation of cyclin-dependent kinases (CDKs) results in
the inactivation of the brake, Rb, by phosphorylation
Phosphorylated Rb releases the S phaseregulating transcription
factor, E2F/DP1, and genes required for S phase progression are
expressed
THANK YOU!
YANNIE SAN-ANTONIO
KAT KABIGTING
KIMPOY SEVILLA
FRECHELLE DY
FARA LUIS
JONATHAN DE LUNA