Define cancer and Describe cell cycle. Able to demonstrate the risk factor, character , diagnosis and treatment of cancer Able to understand the warning signs of cancer. List the anti cancer drug classification. Able to demonstrate the mechanism of cancer drugs. Describe the toxic effects of anti cancer drugs. Cancer is the rapid creation of abnormal cells that grow beyond their usual boundaries, and which can then invade adjoining parts of the body and spread to other organs. This process is referred to as metastasis. Metastases are the major cause of death from cancer. (WHO) Cancer known medically as a malignant neoplasm, is a broad group of diseases involving unregulated cell growth. In cancer, cellsdivide and grow uncontrollably, forming malignant tumors, and invading nearby parts of the body. The cancer may also spread to more distant parts of the body through the lymphatic system or bloodstream. Not all tumors are cancerous; benign tumors do not invade neighboring tissues and do not spread throughout the body. There are over 200 different known cancers that affect humans.

1. Anti Cancer Drugs
By: SWETA MAURYA

2. Content
• Introduction
• Mode of action
• Synthesis
• Cancer Threapy

3. AntiCancer
Drugs
• Mode of action
• Synthesis
• Mercaptopurine
• Cyclophosphamide
• 5 Flurourocil
• Cancer Threapy
• Hormone Threapy
• Gene Threapy
• Natural Products

4. LEARNING OUTCOME
1. Define cancer and Describe cell cycle.
2. Able to demonstrate the risk factor, character ,
diagnosis and treatment of cancer
3. Able to understand the warning signs of cancer.
4. List the anti cancer drug classification.
5. Able to demonstrate the mechanism of cancer drugs.
6. Describe the toxic effects of anti cancer drugs.

5. INTRODUCTION/
DEFINATION
Cancer is the rapid creation of abnormal cells that grow
beyond their usual boundaries, and which can then
invade adjoining parts of the body and spread to other
organs. This process is referred to as metastasis.
Metastases are the major cause of death from cancer.
(WHO)

6. Cancer known medically as a malignant neoplasm, is a
broad group of diseases involving unregulated cell
growth.
In cancer, cellsdivide and grow uncontrollably, forming
malignant tumors, and invading nearby parts of the
body.
The cancer may also spread to more distant parts of the
body through the lymphatic system or bloodstream.
Not all tumors are cancerous; benign tumors do not
invade neighboring tissues and do not spread
throughout the body.
There are over 200 different known cancers that affect
humans.

7. EPIDEMIOLOGY OF CANCER

8. RISK
FACTORS
1. Tobacco
2. Sunlight
3. Ionizing radiation
4. Certain chemicals and other substances
5. Some viruses and bacteria
6. Certain hormones
7. Family history of cancer
8. Alcohol
9. Poor diet, lack of physical activity, or being
overweight

9. CHARACTERISTIC
OF CANCER
Cancer arises as a result of a series of genetic and
epigenetic changes, the main genetic lesions being:
oinactivation of tumour suppressor genes
othe 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:
ouncontrolled proliferation
oloss of function because of lack of capacity to
differentiate
oinvasiveness
othe ability to metastasise.

10. CHARACTERISTIC
OF CANCER
Cancer cells have uncontrolled proliferation because of
changes in:
ogrowth factors and/or their receptors
ointracellular signalling pathways, particularly those
controlling the cell cycle and apoptosis
otelomerase expression
otumour-related angiogenesis

11. THE SEVEN
WARNING SIGNS
OF CANCER
The American Cancer Society uses the word C-A-U-T-I-O-
N to help recognize the seven early signs of cancer:
Change in bowel or bladder habits
A sore that does not heal
Unusual bleeding or discharge
Thickening or lump in the breast, testicles, or elsewhere
Indigestion or difficulty swallowing
Obvious change in the size, color, shape, or thickness of
a wart, mole, or mouth sore
Nagging cough or hoarseness

12. CANCER TYPES
categorized based on the functions/locations of the
cells from which they originate:
 Carcinoma: a tumor derived from epithelial cells,
those cells that line the surface of our skin and
organs (80-90% of all cancer cases reported)
 Sarcoma: a tumor derived from muscle, bone,
cartilage, fat or connective tissues.
 Leukemia: a cancer derived from white blood cells or
their precursors.
 Lymphoma: a cancer of bone marrow derived cells
that affects the lymphatic system.
 Myelomas: a cancer involving the white blood cells
responsible for the production of antibodies (B
lymphocytes)

13. Go – Resting phase
Restriction checkpoint
8hrs or more
6-8 hrs
2-5 hrs
CELL CYCLE

14. Normal Cell
DNA Damage
Mutations in the genome
of somatic cells
Alteration of genes that
regulates apoptosis
Expression of altered gene products
Loss of regulatory gene product
MALIGNANT NEOPLASM
Activation of
growth promoting
oncogene
Inactivation of cancer
suppressor genes
Acquired
(environmental DNA
damaging agents)
Chemicals
Radiation
viruses
Successful DNA repair
Failure of DNA repair
CARCINOGENESIS
•Clonal expansion
•Additional mutations
•Heterogeneity

15. FORMATION OF MALIGNAT CELL BY MUTATION

16. TREATMENT OPTIONS OF CANCER
• Surgery: before
1955
• Radiotherapy:
1955~1965
• Chemotherapy:
after 1965
• Immunotherapy
• Gene therapy

17. 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)
Example:
CA15-3 - Breast cancer.
CA19-9 - Gastrointestinal tumours.
CA-125 - Ovarian cancers.
PSA - Prostate cancers.

18. CELL CYCLE SPECIFIC /NON- SPECIFIC DUGS

19. ANTI CANCER DRUG CLASSIFICATION

20. ANTI CANCER DRUG CLASSIFICATION WITH CLASS /TYPE

23. CHEMOTHERAPEUTIC DRUGS AFFECTING RNA /DNA PRECURSORS

24. COMPARISON OF
MYELOSUPPRESSIVE
POTENTIAL OF
CHEMOTHERAPEUTIC
DRUGS

25. MECHANISAM
OF
ANTICANCER
DRUGS
Alkylating agents and related compounds, which act by
forming covalent bonds with DNA and thus impeding
replication
Antimetabolites, which block or subvert one or more of
the metabolic pathways involved in DNA synthesis
Cytotoxic antibiotics, i.E. Substances of microbial origin
that prevent mammalian cell division
Plant derivatives (vinca alkaloids, taxanes,
campothecins) -most of these specifically affect
microtubule function and hence the formation of the
mitotic spindle.
Hormones, of which the most important are steroids,
namely glucocorticoids, oestrogens and androgens, as
well as drugs that suppress hormone secretion or
antagonise hormone action.

26.  Methotrexate potently inhibits
Dihydrofolate reductase (DHFR).
 This leads to decreased production of
compounds adenine, guanine and
thymidine and the amino acids
methionine and serine, depletion of
thymidine.
 Finally depressed DNA, RNA, and protein
synthesis and, ultimately, to cell death.
FH2 = dihydrofolate; FH4 = tetrahydrofolate; dTMP = deoxythymidine monophosphate;
dUMP = deoxyuridine mono phosphate.
MECHANISM OF ACTION OF METHOTREXATE

27.  6-Mercaptopurine penetrates target
cells and be converted to the
nucleotide analog.
 This leads to inhibit the first step of
de novo purine-ring biosynthesis
 This results in non-functional RNA
and DNA.
MECHANISM OF ACTION OF 6-MERCAPTOPURINE

28. 5-FU = 5-fluorouracil; 5-FUR = 5-fluorouridine; 5-FUMP = 5-fluorouridine monophosphate; 5-FUDP = 5-
fluorouridine diphosphate; 5-FUTP = 5-fluorouridine triphosphate; dUMP = deoxyuridine monophosphate; dTMP =
deoxythymidine monophosphate. 5-FdUMP = 5-fluorodeoxyuridine monophosphate.
MECHANISM OF ACTION OF 5-FLUOROURACIL
 5-Fluorouracil competes with
deoxyuridine monophosphate for
thymidylate synthase and reduce
the thymidine.
 DNA synthesis decreases due to
lack of thymidine, leading to
imbalanced cell growth.

29.  Gemcitabine inhibits DNA synthesis
by being incorporated into sites in the
the growing strand that ordinarily
would contain cytosine.
 Gemcitabine diphosphate inhibits
ribonucleotide reductase, which is
responsible for the generation of
deoxynucleoside triphosphates
required for DNA synthesis.
MECHANISM OF ACTION OF GEMCITABINE

30.  Doxorubicin and daunorubicin bind to
sugar-phosphate backbone of DNA. This
causes local uncoiling. Which leads to
blocks DNA & RNA synthesis and
catalyzed breakage supercoiled DNA
strands, causing irreparable breaks.
 Catalyzes the reduction of free radicals.
These in turn reduce molecular O2,
producing superoxide ions and hydrogen
peroxide, which mediate single-strand
scission of DNA.
MECHANISM OF ACTION OF DOXORUBICIN AND DAUNORUBICIN

31.  A DNA-bleomycin-Fe2+ complex
appears to undergo oxidation to
bleomycin-Fe3+.
 The liberated electrons react with
oxygen to form superoxide or hydroxyl
radicals, which in turn attack the
phosphodiester bonds of DNA,
resulting in strand breakage and
chromosomal aberrations.
MECHANISM OF ACTION OF BLEOMYCIN

32.  Mechlorethamine is alkylates the N7
nitrogen of a guanine residue in one or
both strands of a DNA molecule This
alkylation leads to cross-linkages
between guanine residues in the DNA
chains and/or depurination, thus
facilitating DNA strand breakage.
 Alkylation can also cause miscoding
mutations.
MECHANISM OF ACTION OF MECHLORETHAMINE

33. MECHANISM OF ACTION OF VINCA ALKALOIDS

34. MECHANISM OF ACTION OF ANTIESTROGEN

35.  Flutamide,nilutamide and bicalutamide are
synthetic, nonsteroidal antiandrogens used in
the treatment of prostate cancer.
 Estrogens, such as ethinyl estradiol or
diethylstilbestrol, had been used in the
treatment of prostatic cancer. However, they
have been largely replaced by the GnRH analogs
MECHANISM OF ACTION OF ESTROGENS IN PROSTATIC CANCER

36.  Tamoxifen binds to the estrogen receptor
and the complex fails to induce estrogen-
responsive genes, and RNA synthesis does
not ensue.
 The result is depletion (down-regulation) of
of estrogen receptors, and the growth-
promoting effects of the
natural hormone and other growth factors
are suppressed.
 The action of tamoxifen is not related to
any specific phase of the cell cycle.
MECHANISM OF ACTION OF TAMOXIFEN

37. Normal unwinding of double helix
Irinotecan and topotecan are inhibit the
unwinding of double helix
MECHANISM OF ACTION OF IRINOTECAN &TOPOTECAN

38. Irinotecan and topotecan are
semisynthetic derivatives.These drugs are
S-phase specific. They inhibit
topoisomerase I, which is essential for the
replication of DNA in human cells.
MECHANISM OF ACTION OF IRINOTECAN &TOPOTECAN

39.  Acute toxicity
o Vomiting
o Allergic reactions
o Arrhythmias
 Delayed effects
o Mucositis
o Alopecia
o Bone marrow suppression
 Chronic toxicities
o Heart
o Kidney
o Liver
o Lungs

40.  Every year, more than 1 million Americans and more than 10 million people worldwide are
expected to be diagnosed with cancer, a disease commonly believed to be preventable.
 Only 5–10% of all cancer cases can be attributed to genetic defects, whereas the remaining
90–95% have their roots in the environment and lifestyle.
 The evidence indicates that of all cancer-related deaths, almost 25–30% are due to
tobacco, as many as 30–35% are linked to diet, about 15–20% are due to infections, and
the remaining percentage are due to other factors like radiation, stress, physical activity,
environmental pollutants etc.
 Therefore, cancer prevention requires smoking cessation, increased ingestion of fruits and
vegetables, moderate use of alcohol, caloric restriction, exercise, avoidance of direct
exposure to sunlight, minimal meat consumption, use of whole grains, use of vaccinations,
and regular check-ups.
CONCLUSION

54. Natural Antineoplastic Drugs
 Imides & Amides e.g Colchicine (Alkaloid)
Tertiary Amines e.g. Vinblastine (Indole Alkaloid)
Hetrocyclic Amines e.g. Camptothecin (Chinese tree - Alkaloid)
Lactones e.g. Podophyllotoxin (Himalayan Shrub - Alkaloid)
Glycosides e.g. Camptothecin (Mithramycin)

55. Anticancer Drugs

56. Introduction
The anticancer drugs either kill cancer cells or modify
their growth – but, selectivity of these drugs limited –
damages normal cells too
No Treatment: Before 1940 (Nitrogen mustard)
Rapid progress since then
Surgery: before 1955
Radiotherapy: 1955 - 1965
Chemotherapy: after 1965
Immunotherapy, Hormone therapy , stem cell
transplant and Gene therapy
 Innovations: Target growth factors, specific signaling
pathways, angiogenesis and tumour antigen etc.

57. Aims of Therapy
Cure or induce prolonged ‘remission’ so that all
macroscopic and microscopic features of the cancer
disappear, though disease is known to persist - Acute
Lymphoblastic Leukaemia, Wilm`s tumor, Ewing`s
sarcoma, Retinoblastoma and Rhabdomyosarcome etc.
in children
 Hodgkin`s lymphoma, testicular teratoma,
seminoma and choriocarcinoma etc.
Palliation: Shrinkage of evident tumour, alleviation of
symptoms and prolongation of life - Breast cancer,
ovarian cancer, endometrial carcinoma, CLL, CML, small
cell cancer of lungs and Non-Hodgkin lymphoma
 Insensitive or less sensitive but life may or may not
be prolonged - Cancer esophagus, cancer stomach,
sq. cell carcinoma of lung, melanoma, pancreatic
cancer, myeloma, colorectal cancer

58. Aims of
Therapy
Adjuvant therapy: One of the main basis of treatment
now
For mopping up of residual cancer cells including
metastases after Surgery, Radiation and
immunotherapy etc.
Routinely used now
Mainly in solid tumours – combined modality approach

59. CancerChemotherapy – 5 years survival rate
Childhood Acute Lymphoblastic
Leukemia
50 - 80%
Acute Adult Lymphoblastic Leukemia 20 - 60%
Childhood Acute Myeloblastic
Leukemia
20 - 60%
Adult Acute Myeloblastic Leukemia 10 - 20%
Breast Cancer 5 - 20%
Hodgkin’s lymphoma 40 - 80%
Cancer Chemotherapy – 5 years survival rate

60. General
Toxicities
Harmful to normal tissues – rapidly multiplying cells
(drug targets – nucleic acid synthesis) - particularly to
GI mucosa, Bone marrow, RE system and gonads and
hair cells
Steep dose response curve
Low therapeutic index
Effects are in dose dependent manner

61. Toxicities –
Immunity and
Infections
Bone marrow depression (at therapeutic doses): Agranulocytopenia,
agranulocytosis, thrombocytopenia and aplastic anaemia etc. – Infection and
Bleeding - often limits treatment
Lymphoreticular system: Lymphocytopenia and inhibition of lymphocyte
function – suppression of CMI and humoral immunity
o Epithelial damage + above 2 - - susceptibility to infections
o Fungi – Candida; Viruses – Herpes zoster and CMV; Toxoplasma and
Pneumocystis jiroveci
Oral cavity: Buccal mucosa - High epithelial turnover - stomatitis
o Regular minor trauma to oral mucosa and gums + presence of high oral
microflora + lowered immunity – increased oral infections
o Xerostomia – dental carries
o Bleeding of gums
GIT: Diarrhoea, shedding of mucosa, haemorrhage – decrease in rate of
renewal
o Nausea, vomiting – CTZ direct stimulation and generation of emetic
impulses/mediator from Upper GIT
Skin: alopecia
Gonads: oligospermia, impotence, amenorrhea and infertility
Foetus: Abortion, fetal death and teratogenicity

62. Toxicities –
Immunity and
Infections
Carcinogenicity: leukaemias and lymphomas
Hyperuricaemia: Uric acid- Purine metabolism - Acute
renal failure, gout and lithiasis
Specific toxicities: Neuropathy, myopathy, cystitis,
alopecia etc.

63. Anticancer
Drugs

64. Classification
 According to chemical structure and sources of drugs:
o Alkylating Agents, Antimetabolite, Antibiotics, Plant Extracts,
Hormones and Others
 According to biochemical mechanisms of anticancer action:
o Block nucleic acid biosynthesis
o Direct influence the structure and function of DNA
o Interfere transcription and block RNA synthesis
o Interfere protein synthesis and function
o Influence hormone homeostasis
 According to the cycle or phase specificity of the drug:
o Cell cycle nonspecific agents (CCNSA) & Cell cycle specific
agents (CCSA)
However – They may overall act as Cytotoxic (directly nonspecific
action on cells) or at specific target or Indirectly via Hormone

65. Drugs acting
directly on cells
(cytotoxic drugs)
Alkylating Agent:
 Nitrogen mustards: mechlorethamine,
cyclophosphamide, ifosfamide, chlorambucil, Mephalan
 Ethylenimine: Thio-TEPA
 Alkyl sulfonate: Busulfan
 Nitrosoureas: Carmustine, Lomustine
 Triazine: Dacarbazine, Tremozolomide
 Methylhadrazine: Procarbazine
 Platinum: cis-platinium, carboplatin and Oxaliplatin

66. Drugs acting
directly on cells
(cytotoxic drugs)
Antimetabolites:
o Folate antagonist: Methotrexate (Mtx), Penetrexed
o Purine antagonist: 6-Mercaptopurine (6-MP) and 6-Thioguanine
(6-TG)
o Pyrimidine antagonist: 5-Fluorouracil and cytarabine
Antitubulins: vinca alkaloids (vincristine and vinblastin) and taxanes
(paclitaxel and docetaxel), Estramustine (Bind tubulin, destroy spindle
to produce mitotic arrest)
oTopoismerase-2 inhibitor: Etoposide
oTopoismerase-1 inhibitor: Topotecan and Irinotecan
Antibiotic: Bleomycin, Mitomycin C, Actinomycin D (dactinomycin),
Doxorubicin, Daunorubicin, Epirubicin, Mitoxantrone
Miscellaneous: Hydroxyurea, L-asparginase, Tretinoin, Arsenic trioxide

67. Targeted Drugs
Tyrosine protein kinase inhibitor: Imatinib, Nilotinib
EGF receptor inhibitors: Geftinib, Erlotinib, Cetuximab
Angiogenesis inhibitors: Bevacizumab, Sunitinib
Progesterone inhibitors: Bortezomib
Unnamed monoclonal antibody: Rituximab,
Trastuzumab

68. Influence
hormone
homeostasis
These drugs bind to hormone receptors to block the
actions of hormones which results in inhibition of tumor
growth
Glucocorticoid drug: prednisolone and others
Estrogens and estrogen receptor modulators: (EE,
fosfestrol, SERM-tamoxifene, Toremifene)
Estrogen receptor down regulators: Fulvestrant
Aromatase inhibitor: Letrozole and anastrazole,
Exemestane
Androgen antagonists: Flutamide and Bicalutamide)
Progestogen drug: Hydroxyprogesterone acetate
GnRH inhibitor: Nafarelin, Triptorelin, Leuprorelin
5-ɑ reductase inhibitors: Finasteride, Dutasteride

69. Individual anticancer drugs

70. Alkylating
agents
 Highly reactive carbonium ion intermediate – transfer
alkyl group to cellular macromolecules
 Position 7 of guanine residues – others also (carboxyl,
hydroxyl etc.)
 Results in cross linking/abnormal base pairing/scission
of DNA strands
 Also cross linking of nucleic acid with proteins
 Radiomimetic actions – like ionizing radiation
 Non specific action on cell stages
 Some – CNS stimulant and cholinergic properties

71. Drugs PA MOA ADRs Uses
Mechlorethamine Highly reactive, local
vescicant -
Nausea, vomiting, extravasations - sloughing HL, NHL - MOPP
Cyclophosphamide No local effect – popular and
wide range of action
Active metabolite –
aldophosphamide,
phosphoramide mustard,
Immunosuppressant
Alopecia and cystitis (acrolein) and emetogenic
Chloramphenicol retards metabolism
Solid tumours
Isofosfamide Congener of Cycloph – longer
t1/2
- Haemorrhagic cystitis (mesna is –SH compound),
lesser emetogenic
Broncogenic CA, breast, testicular,
bladder, head & neck, osteogenic
sarcoma
Clorambucil Slow acting – for lymphoid
tissue, not myeloid
Immunosuppressant DOC - Chronic lymphatic leukaemia,
NHL and few solid tumours
Mephalan BM depression, Infection, Diarrhoea, pancreatitis Multiple myeloma
Busulfan For myeolid tissue, not
lymphoid
Hyperuricaemia, pulmonary fibrosis and skin
pigmentation
DOC in CML
Nitrosoureas Highly lipid soluble – wide
range of activity, cross BBB
CNS action – nausea, vomiting, BM depression (6
weeks) …. Visceral fibrosis and renal damage
Meningeal leukaemias, brain cancer
Dacarbazine Activated in liver, methylates
DNA
Nausea, vomiting, flu like symptoms, neuropathy and
myelosuppression
Malignant melanoma, HL
Procarbazine Not classical agent Activated in liver, methylates
and depolymerizes DNA, also
inhibition of nucleic acid
synthesis
Mutagenic and carcinogenic, Male sterility, vomiting,
leucopenia, thrombocytopenia …Weak MAO
inhibitor – sedation, disulfiram reaction with alcohol
MOPP regimen – HL and for brain
tumours

72. Platinum
compounds –
cisplatin,
carboplatin,
oxaliplatin
Hydrolyzed intracellularly to a highly reactive moiety – causes
cross linking of DNA (CTR1 and MRP1)
N7 of guanine residues
Also reacts with –SH of cytoplasm and nuclear proteins
Effects resemble alkylating agents and radiation
Penetrate tissues and excreted slowly unchanged in urine
T1/2 = 72 hours
Uses: Metastatic testicular and ovarian tumours – also in lung,
bladder, esophageal, hepatic, gastric etc. solid tumours
ADRs: Highly emetic, renal impairment – hydration required;
also ototoxic and neurotoxic
Carboplatin – 2nd generation and oxaliplatin – 3rd generation

73. Antitubulins
Vinca alkaloids (Vinca rosea or
Catharanthus roseus)
 Binds to microtubular protein –
tubulin – prevents its polymerization
– cause disruption of mitotic spindle
and interfere with cytoskeletal
function
 Chromosomes fail to move apart
during mitosis – metaphase arrest
 Vincristine – remission of childhood
acute lymphoblastic leukaemia
 Also AML, WT, HD
 ADR: Neuropathy and alopecia; also
paralytic ileus, postural hypotension,
urinary retention
 Vinblastin – With other drugs in HD,
Kaposi sarcoma, NHL, breast and
testicular cancer
Taxanes – Western yew tree
 Binds to β-tubulin and enhances its
polymerization – microtubules are
stabilized and depolymerization is
prevented
 Stability results in inhibition of
normal dynamic reorganization of the
microtubule network for interphase
and mitoticfunction - Abnormal
microtubules are formed
 Paclitaxel – Metastatic ovarian and
breast carcinoma – after failure of 1
st
line therapy
 Also in small cell lung cancer,
esophageal adenocarcinoma etc.
 Myelosupression and “stocking and
gloves” neuropathy

74. Antibiotics –
Actinomycin D,
Daunorubicin
etc.
Actinomycin D
(Dactinomycin): Potent
antineoplastic
Highly effective in Wilm`s
Tumour and chilodhood
rhabdomyosarcoma
Also in Mtx resistant
choriocarcinoma, Ewing`s
sarcoma, metastatic
testicular carcinoma
MOA: Blocking of RNA
transcription by interfering
with template function of
DNA – also single strand
break in DNA (dactinomycin)
ADRs: Vomiting, stomatitis,
diarrhoea, erythema,
desquamation of skin
Daunorubicin: Limited to acute
myeloid and lymphoblastic
leukaemia
Doxorubicin: Also effective in
many solid tumours – breast,
lung, sarcoma, thyroid, ovary,
bladder
MOA: Intercalate between DNA
strands – block DNA and RNA
synthesis; also strand breakage
of DNA
Toxicity: Cardiotoxicity –
arrhythmia and hypotension –
ECG; also CHF
Also mutagenic and
carcinogenic

75. General
Principles of
Chemotherapy
of Cancer
1. Analogous with Bacterial chemotherapy – differences are
Bacterial metabolism differs from host – but malignant cells not
much different - Selectivity of drugs is limited – because “I may
harm you” – lately - (antigens, oncogenes – CML tyrosine protein
kinase gene)
Microorganisms are amenable to immunological and other host
mechanism; Interferon, Interleukins, TNF etc.
2. A single clonogenic malignant cell can produce progeny – kill
host. All malignant cells must be killed or removed
3. Subpopulation cells differ in rate of proliferation and susceptibility
to chemotherapy – 1st order kinetics – certain fractions of cells are
killed
4. Drug regimens or combined cycle therapy to minute residual
tumour cells after radiation or surgery – effectively palliate large
tumour burden (Basis of treatment now) – combined modality
5. Complete remission should be the goal – used in maximum
tolerated dose
6. Formerly one drug – now 2-5 drugs in intermittent pulses - Total
tumour cell kill – recovery time for normal cells in between

76. Combination
chemotherapy
- synergistic
Drugs which are effective when used alone
Drugs with different mechanism of action
Drugs with differing toxicities
Drugs with different mechanism of toxicities
Drugs with synergistic biochemical interactions
Optimal schedule by trial and error method
Kinetic scheduling: on the basis of cell cycle specificity
(CCS)/non specificity (CCNS)

77.  DARK BLUE LINE: Infrequent scheduling
of treatment courses with low (1 log kill)
dosing and a late start prolongs survival
but does not cure the patient (i.e., kill rate
< growth rate)
 LIGHT BLUE LINE: More intensive and
frequent treatment, with adequate (2 log
kill) dosing and an earlier start is successful
(i.e. kill rate > growth rate)
 GREEN LINE: Early surgical removal of the
primary tumour decreases the tumour
burden. Chemotherapy will remove
persistent secondary tumours, and the total
duration of therapy does not have to be as
long as when chemotherapy alone is used.
Approaches to Drug Treatment

78. THANK YOU