This document discusses several key issues related to chemotherapy for cancer patients. It notes that chemotherapy should only be used after cancer diagnosis is confirmed via biopsy or cytology. It also discusses assessing patient factors like disease extent and tolerance for treatment side effects. The document outlines different levels of chemotherapy sensitivity for various cancer types from highly sensitive to chemo-resistant. It emphasizes restricting chemotherapy to situations where an objective response can be assessed.

1. Prof. Dr M. C. BANSAL
M.B .B.S. FRCOG. MRCOG

2.  Chemotherapy should be restricted to the patients
in whom diagnosis of cancer has been confirmed
by either biopsy or cytology .
 All chemo-therapeutic agents have potential side
effects, and it is important to ascertain whether
the patient has measurable disease and / or
elevated tumor markers ,
 Particularly before starting therapy in patients
with metastatic disease , so that response can be
assessed objectively.

3. ISSUES TO BE DISCUSSED
1. Natural History of the Particular Malignancy
a. Diagnosis of a malignancy made by biopsy
b. Rate of disease progression
c. Extent of disease spread
2. Patient's Circumstances and Tolerance
a. Age, general health, underlying diseases
b. Extent of previous treatment
c. Adequate facilities to evaluate, monitor, and treat
potential drug toxicities
d. The patient's emotional, social, and financial
situation

4. ISSUES TO BE DISCUSSED
3. Likelihood of Achieving a Beneficial Response
a. Cancers in which chemotherapy is curative in some
patients (e.g., ovarian germ cell tumors)
b. Cancers in which chemotherapy has demonstrated
improvement in survival (e.g., epithelial ovarian
cancer)
c. Cancers that respond to treatment but in which
improved survival has not been clearly demonstrated
(e.g., metastatic cervical cancer)
d. Cancers with marginal or no response to
chemotherapy (e.g., melanoma)

5.  To achieve complete cure.
 To achieve best possible survival.
 To relieve agony by palliation in terminal
cases.
 To Prevent recurrence.
 To reasonably reduce distant and regional
metastasis and if present, to treat them.
 To improve result of surgery , radiotherapy
and immunotherapy.
 To minimize the side effects

6. 1. Highly chemo sensitive - curative results.
Ovarian germ cell, gestational trophoblastic tumor.
2.Chemosensitive - cure is uncommon .
Epithelial cancer of ovary with 70-89% response but
most patients will have relapse. Chemotherapy
improves survival but does not restore a normal life
expectancy.
3.Low sensitivity - Uterine leiomyo-sarcoma impact of
therapy over survival rate is not clear.
4.Chemo resistant - metastatic melanoma, low or
unpredictable response.

7.  Chemo therapeutic agents must have greater activity
against tumor cells as compared to normal tissue, thus
cause less toxicity and possess wider therapeutic
window.
 Most chemo therapeutic agents act by disturbing
DNA or RNA synthesis, affecting crucial enzymes or
altering protein synthesis.
 Normal cell growth also uses similar vital pathways
as the malignant cells, particularly regenerating
normal cells i.e. GIT mucosa , bone marrow, hair
follicles, skin etc..
 Hence differential sensitivity of anti neoplastic drugs
by normal VS tumor cells is quantitative rather than
qualitative.

8.  Therapeutic Index =
Ratio of drug dose needed for
Therapeutic effect and drug dose which
will result in toxicity.
Because window of toxicity is very narrow
for available drugs , useful therapeutic
response depends on pharmacology and
biological factors.

9.  1. Cell cycle.
 2. Pattern of normal growth
 3. Cell Kinetic Concepts
 4. Cancer cell growth.

10. Cell Cycle
M-mitotic phase-
phase of division.
G1-Post mitotic Phase –
differentiation or continue in
proIiferation.
S phase-DNA synthesis phase –
New DNA Replication occur
G2Phase-postsynthetic phase
Cell has diploid
No of chromosomes,
Twice DNA Content of
normal cell.
G0 phase-resting phase.
Cells do not divide.
Cell may move in or out of
the G0 phase.

11.  Generation time is duration of
cycle from M phase to M phase.
 Variation occurs in all phases of cell
cycle , but it is maximum in G0
phase.
 Causes of variation are complex and
not completely understood.
 Dividing cells that are actively
traversing the cell cycle are most
sensitive to chemotherapy.

12. All normal tissues have the capacity for cellular division and
growth . There are 3 general types of normal cell growth 
 1. Static population comprises of relatively well
differentiated cells that after initial proliferative activity
in embrionic and neonatal period , rarely under go cell
division like striated muscle and neurons.
 2. Expanding Cell population is characterized by
ability to divide under special circumstances e.g. tissue
injury stimulate growth in liver and kidney.
 3. Renewing Population of cells is constantly in
proliferative state .cell division is constantly going on.
There is high degree of tissue turnover and cell loss ., this
occurs in bone marrow, skin, GI mucosa etc.

13.  Only small proportion of tumor cells are in active
cell division at any time.
 2 major factors that affect the rate at which growth
occurs — (a) Growth Fraction (b) Cell Death.
 (a) Growth Fraction No. of tumor cells that are
actively and rapidly dividing , ranging from
25 - 95 % of cell mass. Cancer Stem cells make a
very small population of tumor, these are
relatively chemo- resistant . These stem cells play
an important role in the development and
progression of tumor growth even after
chemotherapy is stopped.

14. Tumor growth may be altered in following
ways 
1. Cytotoxic chemotherapy-- alters both generation
time and growth fraction of tumor.
2. Hormones—alter the growth fraction, have no
effect on generation time.
3. Radiation therapy--alters both growth fraction
and generation time.
4. Altering O2 tension and Vascular supply--alter
growth fraction only.
5. Immunotherapy-- it alters both .

15.  Cell Cycle : specific / non specific agents
 Cell cycle - Non specific agents - Kill the cell in all
phases of cycle and are not too dependent on cellular
division or proliferation.
 Cell cycle - specific agents – Hydroxyurea , its cell
killing effect depends on cell proliferative activity .
They kill in only one phase of cell cycle - most active in
S phase.
 In addition to cell cycle and proliferative sensitivity;
different chemo therapeutic drugs may exert a greater
effect, in different phases of cell cycle, hence
combination of various chemo therapeutic agents may
give greater killing effect on tumor cells with reduced
toxicity, as compared to single drug treatment.

18.  Tumor cell growth represents a disruption in the
normal cell growth check / control mechanism
resulting in continued proliferation at the cost of
normal cell and eventual death of host.
 Gompertzian growth this means exponential
growth spurt and exponential growth
retardation over entire duration of tumor growth
e.g. as the tumor size increases rapidly then the
time required in doubling its size also increases.

19.  Doubling Time of tumor is the time taken by
tumor to enlarge to double it’s size. For example
Embyronal tumors, lymphomas and some
mesenchymal cancers have relatively fast
doubling time (20-40 days) in comparison that of
Adeno / Squamous cell carcinomas ( 50-150 days).
 In general metastasis have faster doubling times
than primary tumor.

20.  It is assumed that a tumor starts from a
single malignant stem cell, then exponential
growth occurs at an early stage.
 1. a 1-mm will have under gone
approximately 20 tumor doublings.
 2. a 5 mm size tumor ( first time might be
identifiable on a radiograph) will have under
gone 27 doublings.

21.  3. a 1 cm tumor mass will have undergone
30 doublings.
 Once tumor is palpable or detectable (1cm
in diameter) then 3 more doublings will
produce a mass measuring 8 cm.
 Metastasis have usually taken place by this
time. That is why patient seeks medical
consultation at late stages and currently
available diagnostic methods detect
tumour growth in late stage only

22.  Chemo therapeutic drugs appear to work by 1st
order kinetics , that is , they kill a constant fraction
of cells rather than a constant number.
 The cure rate will be significantly increased if
tumor mass is small, but cell masses of 1o raise to
power one to 10 raise to power four cells are too small
to detect clinically.
 This is the basis of using adjuvant chemotherapy in
early stage of disease when sub clinical metastasis
are likely to be present in many patients.

23.  Chemotherapeutic agents are best effective when
initially used in cancer treatment.. Later the tumor
develop resistance and tumor cell killing effect is
blunted . Hence patient often have initial remission
followed by recurrence after variable time interval.
 Various mechanisms operate in development of drug
resistance.
 Resistant tumor may display increased rate of drug
deactivation or decreased killing activity of
drug., increased drug efflux, or decreased drug
intake by tumor cells.
 Altered efficacy of inhibiting enzymes , or increased
production of drug target enzymes occur to explain
the development of drug resistant after some time.

24.  Goldie Coldman Hypothesis : The proportion of resistant
cells in any untreated tumor is likely to be small , and the
initial response to treatment will not be influenced by the
small number of resistant cells. Hence remission can be
achieved initially even though the resistant cells are
present in tumor.
 This model of spontaneous resistance implies that 
1. Tumors are curable with chemotherapy if no
permanently resistant cells are present or drug therapy is
begun before resistance develop.
2. If only one antineoplastic drug is used , than probability
of cure diminishes rapidly with development of a single
resistant line.

25. 3. Minimizing the development of drug resistant
clones
require multiple effective drugs at the time of
starting
treatment.
4.The rate of spontaneous mutation to resistant
occurs naturally at the frequency of 1 in 10,000 to 1
in 1,ooo,ooo.cell division.
This model predicts that alternative cycles
of treatment should be superior to sequential use
of particular drug because sequential use of
antineoplastic agent would allow for development
of resistance and regrowth of doubly resistant
line.

26. It focuses on the Gompertzian growth rate exhibited by
malignant tumors.
It suggests that treatment of cancer cells exhibiting sensitivity to
particular chemotherapeutic agents will be enhanced if single or
multiple drug regimens are delivered at their optimal dose
levels in so called in a dose dense manner rather alternating
regimens.
High risk gestational trophoblastic tumors are very sensitive to
EMA-CO every 6to 7 days is an example of dose dense regimen.
The difference between two is---
1.Goldi Coldman focusses on rapid administration of as
many active agents as possible, doses of individual agent
need frequent modification because of overlapping drug
toxicities.
2.Nortonand Simon theory---individual drugs are given in
sequence at their optimal dose to produce their cytotoxic
effect

27.  Itoccurs when certain drugs
develop cross resistance even
of being dissimilar in their
pharmaceutical structure and
different mechanism of
action.

28.  Studies in human solid tumors in vitro frequently
demonstrate steep dose response curves suggesting
the importance of giving full dose .
 Several prospective randomized studies in epithelial
ovary tumors have failed to demonstrate improved
results either by increasing dose of cisplatin or
Carboplatin per cycle or extending the duration of
treatment beyond 5-6 cycles.
 In general , the goal should be to maintain dose
intensity consistent with acceptable toxicity profile
on each individual patient.

29. Drug effect = Drug concentration x durn of exposure
= C (plasma concentration) x T (Time)
Factors
1.Route of administration & absorption.
2. Transportation and drug distribution.
3.Drug metabolism, biotransformation.
4.Inactivation and Excretion.
5.Drug interactions

30.  Drug may be given orally, IM, IV, intra cavitary
, intra tumor , regional
 Studies of wide variety of chemotherapeutic agents
have demonstrated a differential concentration of
30- 100 fold , depending on molecular weight
, charge and lipid solubility of agent.
 Several studies have revealed that intra peritoneal
administration of Cisplatin as a primary therapy in
cases of small volume advanced ovarian cancer is
highly effective

31.  Antineoplastic drugs produce their antitumor
effect by interacting with intracellular target
molecules.
 It is critically important that drug in its active form
should reach in side the cancer cell in appropriate
concentration.
 After absorption from the site of administration
, drugs may be bound to albumin or other blood
components, their ability to enter various body
compartments , vascular spaces, and extra cellular
sites is highly influenced by plasma protein
bindings, relative ionization at body fluid’s pH
, molecular size and lipid solubility.

32.  Sanctuary Site These are areas where the tumor
is inaccessible to anticancer drug., hence ineffective
like CSF, center of large tumor masses (avascular).
 Cell Penetration it may be by simple diffusion
or by active transportation across cell membrane.
Alkylating drugs depend on a carrier transport for
cellular penetration . For Macromolecules it may
be necessary for pinocytosis to accomplish cellular
entry.

33.  Mani drugs are active as intact molecule but some
require metabolism / transformation to active form.
 Many anti metabolite drugs need phosphorylization for
cell entry.
 Alkylating agent Cyclophsphamide requires absorption
and liver metabolism to be activated , while thiotepa or
nitrogen mustard need no metabolism for activation .
Not only initial activation is important but rate of
metabolic degradation of active drug or its active
metabolite form is important in determining antitumor
activity . Eg. is increased intracellular enzymes
(glutothione-s-Transferase) hasten the degradation of
metabolites of Alkylating drugs - development of drug
resistance in short time .

34.  Most chemotherapeutic drug or their metabolites
are excreted by kidney or liver ., their normal
function are critical to normal drug excretion
thereby minimizing side effects.
 Vincristn, Doxorubicin,Paclitaxel are excreted
primarily and exclusively by liver.
 while other drugs like Methotrexate is
excreted almost entirely by the kidney.

35.  Drug interaction may increase or decrease the antitumor
activity of a particular drug or they may increase or
modify its toxicity.
 Important drug interactions are -
1.Alkylating agents are highly reactive compounds and
may produce direct physical or chemical inactivation
when multiple drugs are used .
2.Intestinal absorption of drugs is altered by concurrent use
of oral antibiotics that suppress bacterial flora , example
Methotrexate.
.

36. 3.Cisplatin / methotrexate bound to albumin and
may be displaced from their binding site by drugs
like aspirin and sulfa , thereby increasing free and
higher concentration of these anticancer drugs -
increased toxicity .
4.Alteration in drug interaction may occur , as when
methotrexate increases 5 fluorouracil activation.,
while % fluorouracil impairs the antifolate activity
of methotrexate.
5.Nephrotxic antibiotics frequently alter
methotrexate excretion and may increase renal
toxicity of cisplatin.

38.  Sound basis for combination chemotherapy is from
knowledge of cellular kinetics , drug metabolism , drug
resistance and tumor heterogeneity.
 Limitations of Single drug therapy
1. Toxicity limits the dose and duration of drug
administration thus restricts the tumor cell kill
achievable.
2. Adaptive mechanism allow cell survival and
eventual tumor regrowth of drug resistant tumor
cells in spite of initial lethal effect on bulk of tumor
mass.
3. Drug resistance may develop spontaneously.
4. Multi drug or Pleiotropic drug resistance may
develop.

40.  Different chemotherapeutic agents may act in
different phases of tumor cell cycle. With
identification of appropriate combinations and
proper dose schedule and sequence, sufficient log
kill can be achieved.
 Drug Resistance  Probability of emergence of
drug resistance cells have reduced if 2or more
drugs with different mechanism of action are used
in tight sequenced treatment scheme .

41. DRUG INTERACTION  It may be
additive, synergistic or antagonistic.
Additive therapy produce enhanced
antitumor effect equivalent to sum of
actions of combined drugs.
Combination that results in improved
therapy due to increased antitumor action
and decreased toxicity are said to be
synergistic .

42. SCHEDULE DEPENDENCY = Drugs used in
different sequence may produce a widely varied
effect, example is the reduced cardiac toxicity when
weekly low dose Doxorubicin compared to high
bolus dose.
REMISSION  Complete remission (response) with
significant prolongation of survival.
Partial / Incomplete remission (response) : 30-50%
reduction in size of tumor along with variable
subjective improvement and absence of new lesion
development during therapy.

43. RECIST : DEFINITION OF RESPONSE

44. Dose (mg)
=
target AUC
x
sum of GFR + 25 %
(AUC is area under curve)

45. DRUG DOSE ADJUSTMENT – COMBINATION CHEMOTHERAPY
SLIDING SCALE BASED ON BONE MARROW TOXICITY

46.  Antitumor drugs are most toxic agents used in
modern medicine.
 Mechanism of toxicity is similar to their killing action
on neoplastic cells.
 Organ systems which are rapidly proliferating as a
normal physiological phenomenon are most
affected.,e.g. skin, hair, bone marrow , GI mucosa .
 Even organs with limited cell devison may be
affected either dose related or idiosyncratic fashion.
 Severe debility, advanced age, poor nutritional
status, direct involvement of organ system can result
in unexpectedly severe side effects.

47.  The proliferating cells of erythroid, myeloid,
megakaryocytic series of bone marrow are highly
susceptible to damage by commonly used anti-
neoplastic agents.
 Granulocytopenia develops with in 6 -12 days and
recovery occurs in 3-4 weeks, while
thrombocytopenia develops 4-5 days later , with
recovery after white cell recovery.
 Patient with absolute granulocyte count <500/cmm
for 5 days are prone to have sepsis . Quickly
initiating broad spectrum antibiotics in presence of
fever can be a wise policy

48.  Platelets count < 50,00 are at risk of spontaneous
bleeding particularly from GIT or intracranial hge.
 Platelet concentrate transfusion is indicated 
1. If patient manifests active bleeding
2. If patient has active peptic ulcer.
3. Before and during surgical procedure.
Recombinant interleukin 11 can be used in patients
with or anticipated to develop, severe
thrombocytopenia. Drug is administered 50 ug / Kg
Sc once a day till platelet count return to > 50,000 /cmm
It is discontinued at least 2 days before next
chemotherapy.

49.  Mucositis - 2-3 days before myelo-
suppression. Increased bacterial and fungal
infection leading to septiceamia.
 Oral candidiasis/ herpes simplex infection.
 Esophagitis , GIT Hemorrhage.
 Impaired intestinal motility(Resulting from
neuropathic effect of vinca alkaloids ).
 Nausea and vomiting.
 Necrotizing enterocolitis - Severe
Diarrhoea, illness that can be fatal in a
granulocytopenic patient.

50.  Most anti cancer drugs are capable of
suppressing immune (Cellular as well as
humoral) system , later being less affected.
 Most of immune suppression effects do not
persist beyond 2-3 days after completion of
chemotherapy.
 This short term immunosuppressive effect
has led to increased use of intermittent
chemotherapy course regimens to allow
immunologic recovery during courses of
treatment.

51.  Skin necrosis and sloughing may result from
extravasation of certain irritating agents , such as
actinomycin-D, mitomycin , vincristin , vinblastin
and nitrogen mustard.
 Alopecia is most common side effect.
 Generalized allergic skin reaction.
 Liposomal Doxorubocin, an agent is effective in
platinum refractory cases of ovarian cancer. It can
produce a painful acute dermatological syndrome
characterized by desquamation of the skin , most
often of feet and hands . Focal or disseminated
blistering may also develop.

52.  Increase in SGOT, SGPT, Alkaline/ Acid
Phosphatase and serum bilrubin is common with
most chemotherapeutic agents. These enzymes
return to normal level after stopping drug
administration.
 Long term use of methotrexate may cause liver
fibrosis – progress to cirrhosis.
 Pre existing liver disease / exposure to hepatotoxins
can increase risk . Antimetabolites like
mercaptopurine , 6-thioguinine can cause reversible
cholestasis.

53.  Respiratory compromise resulting from lung
metastasis , embolism , infection , radiation
pneumonitis and tumor/ drug induced
neuromuscular dysfunction etc may be significant
complications.
 Interstitial Pneumonitis with pulmonary fibrosis is
the usual pattern of lung damage associated with
chemotherapy . Agents likely to cause it are
bleomycin , gemcitabin , nitrosurea.
 Management of drug induced interstitial
pneumonitis includes discontinuation of drugs
, supportive care and steroids.

54.  Anthracyclines and paclitaxel can cause
cardiac arrhythmias.
 Doxarubicin and daunomycin can cause
severe cardiomyopathy.
 massive dose of cyclophosphamide can cause
cardiotoxicity.
 5 flurouracil can cause angina pectoris.
 A major toxicity of the angigenic agent
bevacizumab is development of hypertension.

55.  In addition to anti cancer drugs , other cancer related
complications may produce chronic azotemia, acute renal
failure, including body fluid
depletion, infection, metastasis , ureteral
obstruction, radiation damage and tumorlysis syndrome.
 Drugs that can cause impaired renal function are 
cisplatin produce renal tubular toxicity, methotrexate can
precipitate in tubules causing in acidic pH , nitrosourea
cause chronic interstitial nephritis , mitomycin causes
systemic microangiopathic hemolysis - Ac. Renal failure.
 Metabolites of cyclophosphamide irritate bladder
mucosa - hemorrhagic cystitis . N-acetylcystine or mesna
along with cyclophosphamide is used to prevent cystitis
E –aminocapric acid can also be used.

56.  Vinca alkaloid therapy is associated with
reversible motor , sensory, autonomic
neuropathy.
 Cisplatin cause progressive
ototoxicity, peripheral neuropathy and rarely
retro bulbar neuritis.
 Paclitaxel - peripheral sensory neuropathy.
 5-flurouracil - acute cerebellar toxicity.
 Vit. B supplementation - improve the
neuropathies but decrease the drug
effectiveness.

57.  Anaphylactic reaction has been associated
with cyclophposphamide , cisplatin
, doxorubicin , melphalan , etopside
, teniposide and high dose methotrexate .
 It can be ameliorated with IV
Dexamethasone
(20mg), diphenylhydramine(50mg) and 1:
1000 diluted subcutaneous injection of
Adrenalin.

58.  Many anti cancer drugs are mutagenic and
teratogenic.
 Have profound and lasting effect on
testicular and ovarian function.
 Male develop testicular dysfunction - oligo /
azoospermia.
 Onset of premature ovarian failure -
amenorrhoea elevated FSH , LH levels and
decreased serum estrogen.

59.  Inappropriate Antidiuratic Hormone secretion -
results in electrolyte and fluid imbalance
documentable by 1.Hyponatremia 2.Hypertonic
urine (more than plasma). Exclusion of
hypothyroidism and adrenal insufficiency.
 Hyperuricaemia—when rapid tumor lysis is
occurring it releases intracellular ions and uric acid
resulting in life threatening hyper kalemia
hyperphosphataemia , hypocalcaemia and acute
renal failure. Hyperuricaemia can be prevented by
maintenance of high urinary out put , high urinary
pH(above 7.0) and prophylactic use of xanthine
oxidase inhibitorAllopurinols

60.  Many antineoplatic agent s are mutagenic
and teratogenic.
 Alkaylating agents seem to be major offender
in developing another malignancy .
 High risks are associated with 
1. Extensive radiotherapy along with
chemotherapy.
2. Prolonged alkylating drug therapy > 1year.
3. Age > 40 years at initial treatment.

61.  Risk of congenital malformation ,
 Abortion is highest in 1st trimester.
 Chemotherapy given during 2nd and 3rd trimester is
usually not associated with malformation of fetus.
 Its ill effect on physical and intellectual growth of
fetus ??

62. 1 . Alkylating Agents.
2 . Anti Tumor Antibiotics.
3 . Anti Metabolites.
4 . Plant Alkaloids.
5 . Topoisomerase-1 Inhibitors.
6 . Other Agents.
7 . Miscellaneous Agents.
8 . New Drug Trials.

63. ALKYLATING AGENTS USED IN GYNAECOLOGICAL CANCERS

64. ALKYLATING AGENTS USED IN GYNAECOLOGICAL CANCERS

65.  These agents act primarily by chemical binding
with DNA , they react with nucleophillic (electron
rich) site on many important organic compounds
such as nucleic acid, proteins and amino acids.
These interaction produce cytotoxic effects.
 Mechanism of action Alkylating agents commonly
bound to N-7 position of Guainine and other Key
DNA sites . They interfere with accurate base
pairing , cross linkage of DNA , produce single or
double standard breaks, inhibiting DNA, RNA
and protein synthesis required for cell
proliferation and growth.

66. ALKYLATING – LIKE AGENTS USED IN GYNAECOLOGICAL CANCERS

67.  These are antibiotics , isolated as natural products
from Fungi. They act by forming complex with
DNA.
 Mechanism of action
Antibiotics get inserted between DNA base pairs.
Production of free radicals capable of damaging DNA
RNA and vital proteins essential for cell proliferation
and growth.
Thirdly they cause metal ion chelation and alterations
in cell membrane .
These are ― cell cycle nonspecific Drugs.―

68. ANTI-TUMOUR ANTIBIOTICS USED IN GYNAECOLOGICAL CANCERS

69. ANTI-TUMOUR ANTIBIOTICS USED IN GYNAECOLOGICAL CANCERS

70.  Interact with vital intra cellular enzymes .Their
structure resembles purines and pyrimidines .
 Some of them act directly as intact molecule while
other need biotransformation into active compound.
Mechanism of action
Many drugs act in different ways at different sites in
biosynthetic pathways. There by interfering with cell
function crucial to viability of cells particularly the
actively proliferating cells.

72.  Derived from plant Vinca Rosea are vinca
alkaloids,.have single methyl group on one side chain.
 Plaxitaxe and epipodophyllotoxins are also used in
treatment of gynaecological cancers.
 Like most natural compound complex thesse are large
and molecules.
Mechanism 
Vincristin and vinblastin act by binding to vital
intracellular proteins particularly to Tubulin. It inhibits
microtubule assembly and destruction of mitotic
spindle, cell mitosis is arrested. These are cell cycle specific
agents .
Paclitaxel combines with microtubules resulting in
polymerization and destabilization , disruption of their
function and cell death.

73. PLANT ALKALOIDS

74. PLANT ALKALOIDS

75.  These compounds exert their cytotoxic
effect through inhibition of enzyme
topoisomerase-1.
 It is important enzyme in DNA
replication , repair and transcription.
 Agent binds to enzyme –DNA complex
leading to permanent strand breaks and
cell death.

76. TOPO-ISOMERASE – 1 INHIBITORS

77.  Anti angiogenic drugs like
bevacizumab exert their effect
on normal / abnormal blood
vessel delivering nutrients to
malignancy.

78. MISCELLANEOUS AGENTS

79.  Phase 1 trial These studies define spectrum of
toxicity of any chemotherapeutic agent and are
complete when the dose limiting toxicity of any
particular dose and schedule has been defined.
 Phase 2 Trials  studies usually use the dose and
schedule established from phase 1 trials and apply
this to selected tumor types of importance.
 Phase 3 These studies compare one effective
treatment with another in a randomized
fashion