This document summarizes cancer chemotherapy and the various classes of chemotherapeutic drugs. It describes the mechanisms of action, indications, and side effects of alkylating agents, antimetabolites, plant alkaloids, antibiotics, and other classes of drugs. The principles of cancer chemotherapy are to arrest tumor progression by causing cytotoxicity or apoptosis in cancer cells, often targeting DNA or metabolic pathways essential for cell replication. Drugs are generally used in combination to achieve maximal cell killing while remaining within a tolerable toxicity range.

1. CANCER CHEMOTHERAPY

2. • CANCER: is disease characterized by loss in
normal control mechanism’s that govern cell
survival, poliferation and differentiation.
• METASTASIS: is ability of tumor stem cells to
migrate to distant sites in body to colonize
various organs.
• ONCOGENE: mutant form of normal gene found
in naturally occuring tumors w/c when expressed
in non-cancerous cells cause them to behave like
cancer cells.

3. CLASS OF DRUG
Cyclophosphamide
Melphalan
Mechlorethamine
Busulfan
NITROSOUREAS
Carmustine
Streptazocin
TRIAZINES
Dacarbazine
PLATINUM COORDINATION
COMPOUNDS
ANTI-METABOLITES
NITROGEN MUSTARDS
ALKYL SULFONES
ALKYLATING AGENT
DRUGS
Cisplatin
Carboplatin
Oxaliplatin
FOLIC ACID ANTAGONIST
Methotrexate
PYRIMIDINE ANTAGONIST
5-fluorouracil
Cytarabine
Gemcitabine
PURINE ANTAGONIST
6-mercaptopurine
thioguanine

4. NATURAL PRODUCTS
Vinblastine
Vincristine
TAXANES
Paclitaxel
Docetaxel
EPIPODOPHYLLOTOXINS
Paclitaxel
Docitaxel
ANTIBIOTICS
Dactinomycin
Daunorubin
Doxorubicin
Bleomycin
ENZYMES
MISCELLANEOUS AGENTS
VINCA ALKALOIDS
L-asparginase
SUBSTITUTED UREA
DERIVATIVES
Hydroxy urea
PROTEIN TYROSINE KINASE
INHIBITOR
imatinib
INTERFERON’S AND
CYTOKINE
Interferon α, IL 2

5. HORMONES
ADRENOCORTICOSTEROID
S
Prednisolone
ANTIESTROGENS
Tamoxifen
AROMATASE INHIBITORS
Anastrozole
Letrozole
ANTI ANDROGENS
Flutamide
GONADOTROPHIN
RELEASING HORMONE
leuprolide

6. PRINCIPLES OF CANCER
CHEMOTHERAPY
• Cause a lethal cytotoxic event or apoptosis in
cancer cell that can arrest tumor’s
progression.
• Attack is generally directed towards DNA or
against metabolic sites essential to cell
replication. ( E.G DNA and RNA synthesis w/c
have purines and pyrimidines presence).

7. TREATMENT STRATEGIES:
• GOAL OF TREATMENT:
• 1. ERADICATION OF EVERY NEOPLASTIC CELL.
If cure not possible so next step is control of disease
( stop from spreading).
Initially the neoplastic cell is reduced ( either by
surgery / radiation) followed by chemotherapy,
immunotherapy or combination of treatments.
PALLIATION: alleviation of symptoms + avoidance
of life threatening toxicity is goal of advanced
stage cancer.

8. INDICATIONS FOR TREATMENT:
• 1. chemotherapy is indicated when neoplasm are
disseminated and not feasable for surgery.
• 2. also used as supplemental treatment to attack
micrometastases following surgery and radiation
treatment “ ADJUVANT CHEMOTHERAPY”.
• 3. neo adjuvant chemotherapy is given prior to
surgery to shrink cancer.
• 4. maintenance chemotherapy is given in low
doses to assist in prolonging remission.

10. CELL CYCLE
• PODOPHYLLOTOXIN
• BLEOMYCIN
• Mitotic phase ( cell
divides)
• VINCA ALKALOIDS
G2
S
• DNA is replicated
• ANTIMETABOLITES
• PODOPHYLLOTOXIN
M
G1
• Synthesis of
enzymes needed for
DNA synthesis

11. • Rapidly dividing cells are generally more
sensitive to anticancer drugs whereas slowly
proliferating cells are less sensitive.
• G0 phase cell survive most agents.

12. • CELL CYCLE SPECIFICITY OF DRUGS:
• NORMAL CELL and cancer cell both go through
growth cycle difference is in number
• Chemotherapeutic agents effective only against
replicating cells are called “ CELL CYCLE SPECIFIC”
• Antimetabolites
• Bleomycin
• Antibiotics
• Vinca alkaloids
• etoposide

13. • Effective for high growth fraction malignancies as
hematologic cancers.
• NON CELL CYCLE SPECIFIC DRUGS:
• More toxicity in cycling cells but are useful against
tumors that have low % of replicating cells e.g
• Alkylating agents
• Cisplatin
• Nitrosoureas
• Solid tumors + low + high growth fraction
malignancies.

14. TUMOR GROWTH RATE:
• Initially rapid but growth rate decreases as
tumor size ↑.
• This occurs b/c of unavailability of nutrients
and oxygen caused by ↓ blood circulation.

15. TREATMENT REGIMENS AND
SCHEDULING:
• LOG KILL:
• Destruction of cancer cells by chemotherapeutic
agents follow first order kinetics i.e given dose of
drug destroys a constant fraction of cells not
constant number of cells.
• Diagnosis of leukemia made when 109 total
leukemic cells .
• Five log kill means pt becomes asymptomatic ie is
in remission.

16. PHARMACOLOGIC SANCTUARIES:
• Leukemic or other tumor cells sometimes find
sanctuaries in tissues such as CNS where
chemotherapeutic agents cannnot penetrate
require IT drugs to eliminate leukemic cells or
irradiation of craniospinal axis

17. TREATMENT PROTOCOLS:
• Combination drug chemotherapy is more
successful than single drug treatment
• COMBINATION OF DRUGS:
• Cytotoxic agents with different toxicities,
different molecular sites and MOA are
combined.
• Better effects due to potentiated effects.
• If similar toxicity drugs combined dose should
be reduced.

18. ADVANTAGES OF COMBINATION
THERAPY:
• 1. provide maximal cell killing within range of
tolerated toxicity.
• 2. are effective against broader range of cell
lines in heterogenous tumor population.
• 3. may delay or prevent development of
resistant cell lines.

19. TOXICITY
•
•
•
•
•
•
•
•
•
COMMON ADR:
Narrow therapeutic index
Nausea
Vomitting ( anti-emetic)
Stomatitis.
Bone marrow suppression.
Allopecia.
Cardiotoxicity( doxorubicin)
Pulmonary fibrosis( bleomycin)

20. MINIMIZING ADR:
• Megaloblastic anemia caused by methotrexate
can be overcome by FOLINIC ACID (
LEUCOVORIN)
• Neutropenia ( human granulocyte colony
stimulating factor) FILGRASTIM can be given.

21. ALKYLATING AGENTS:
• Highly reactive , transfer their alkyl groups to
imp cellular constituents DNA or RNA at an
electron rich site making them non-functional.
• Alkylation takes place by chemical formation
of (+) charged carbonium ion that reacts with
functional constituents of DNA.

22. NITROGEN MUSTARDS
• MECHLORETHAMINE:
• Hodgkins disease ( 3 and 4 stage)
• MOPP regimen ( mechlorethamine, oncovin,
procarbazine and prednisolone).
• Chronic myelogenous leukemia.
• Chronic lymphoblastic leukemia.
• 10mg vial reconstituted with 10ml 0.9% NACl
given IV.
• ADR: vesicant action.

23. CYCLOPHOSPHAMIDE:
• Converted to 4-hydroxycyclophosph
CyP2B enzyme → in tumor cell cleav
phosphoramide and acrolein
• Phosphoramide mustard is responsib
activity.
• ADR :
• Acrolein causes hemorrhagic cystitis
• Ample fluid should be taken
• MESNA ( mercaptoethane sulfonate)
cystitis traps acrolein.
• allopecia

24. •
•
•
•
•
•
•
USES:
1. malignant lymphomas.
2. Hodgkins disease.
3. neuroblastoma.
4. breast and ovarian cancer.
IV dose 50mg/kg divided dose over 2-5 days.
Orally 1-5 mg/kg for initial and maintenace
treatment

25. NITROSOUREAS:
•
•
•
•
•
•
CARMUSTINE:
Lipid soluble
Useful for brain tumor
Metastatic brain tumor
Hodgkins and non hodgkins lymphoma
DOSE: 150-200mg/m2 given IV for 6 weeks as
single dose

26. PLATINUM COORDINATION
COMPLEXES:
•
•
•
•
Cisplatin
Carboplatin
Oxaliplatin.
MOA: they kill tumor cells in all stages of cell
cycle by binding to DNA and preventing its
replication by forming intrastrand as well as
interstrand crosslinks.

27. •
•
•
•
•
•
USE:
1. non-small cell and small cell lung cancer.
2. esophageal and gastric cancer.
3. head and neck cancer.
4. genitourinary cancer ( testicular + bladder)
Oxaliplatin in advanced colon cancer.

28. •
•
•
•
ADR:
Neurotoxic ( peripheral neuropathy)
Nephrotoxic( reduced by hydration and mannitol)
Carboplatin less nephrotoxic but causes tinnitus
and hearing loss but greater myelosuppression.
• DOSE: 20mg/m2 for 5 days.
• 75-100mg/m2 once over 4 weeks for ovarian
cancer.

29. PROCARBAZINE:
• Is reactive agent that forms hydrogen peroxide
w/c generates free radicals that cause DNA
strand scission.
• KINETICS: orally active penetrates tissues
including CSF
• USE: component regimen for Hodgkins
lymphoma
• ADR: myelosuppressant
• GI irritation

30. ANTIMETABOLITES
• CCS drugs acting primarily in S phase of cell cycle.
• METHOTREXATE:
• MOA: competitively inhibits enzyme
dihydrofolate reductase w/c catalyzes reduction
of dihydrofolate to tetrahydrofolate→ blocks
synthesis of purines and pyrimidines→ results in
interfering of formation of DNA, RNA and protein
• Polyglutamate derivatives of methotrexate imp
for cytotoxic reactions.

31. • RESISTANCE:
• 1. drug accumulation decreased.
• 2. changes in drug sensitivity or activity of
dihydrofolate reductase.
• 3. decrease formation of polyglutamate.
• KINETICS:
• IV and oral good distribution except CNS.
• Not metabolized clearance depends on renal function.
• Adequate hydration needed to prevent crystallization
in renal tubules.

32. •
•
•
•
•
•
•
USE:
1.choriocarcinoma.
2.acute leukemia.
3.nonHodgkins
4 cutaneous T cell lymphoma.
5 breast cancer
DOSE: 15-30mg/day orally or IV 5 days.

34. •
•
•
•
•
•
•
Meningiocarcinoma given IT.
ADR:
1.mucositis.
2.bone marrow suppression.
3.bloody diarrhea.
4.wt loss.
Leucovorin rescue( tetra hydrofolate is
accumulated more readily by normal cells)
• It bypasses dihydrofolate reductase step in folic
acid synthesis dose 15mg (10mg/m2 every 6 hrly)

35. PYRIMIDINE ANALOGUE:
• 5-FLUOROURACIL:
• Prodrug gets converted to → 5-fluoro-2deoxyuridine (5dump) w/c binds to enzyme
thymidylate synthase and folate cofactors→
covalently preventing formation of thymidylate
and inhibits DNA synthesis.
• 5FU forms Futp ( 5 fluorodine 5 tri phosphate)
w/c is incorporated into RNA where it interferes
with RNA processing and mRNA translation.

36. • USES:
• Treatment of bladder, breast, colon, head and
neck, liver and ovarian cancers.
• DOSE:
• 12mg/kg IV for 4 days.
• 6 mg/kg on alternate days for 4 doses.
• ADR:
• Myelosuppression.
• ALLOPECIA
• jaundice

37. PURINE ANTAGONIST:
•
•
•
•
6-MERCAPTOPURINE:
Thiopurine.
Prodrug
Mercaptopurine in presence of hypoxanthine guanine
phosphoribosyl transferase → thioinosine mono
phosphate (TIMP) → inhibits purine synthesis.
• TIMP → thiguanine mono phosphate and thioguanine
triphosphate .
• Cytotoxic effect of mercaptopurine is result of
incorporation of these nucleotides into DNA.

38. •
•
•
•
•
•
•
•
USE:
1. acute lymphoid leukemia
2. acute myeloid leukemia.
DOSE:
2.5-5 mg/kg once aday.
ADR:
Myelosuppression ( dose limiting)
Hepatic dysfunction ( jaundice)

39. NATURAL PRODUCTS:
• PLANT ALKALOIDS:
• VINCA ROSEA: vincristine, vinblastine and
vinorelbine.
• Cell cycle specific agents blocks in metaphase of
mitosis.
• MOA:
• Binds to tubulin monomers inhibiting formation
of microtubules → without microtubules newly
replicated chromosomes cannot be seperated→
cell division blocked.

40. VINCRISTINE (ONCOVIN)
• USE:
• Acute lymphocytic lymphoma 1.4-2mg/m2 IV at
weekly interval.
• Choriocarcinoma.
• ADR:
• Myelosuppression
• GI mucosal damage
• Allopecia.
• Neurotoxic effects( peripheral neuritis)

41. ETOPOSIDE:
•
•
•
•
Semi-synthetic derivatives of podophyllotoxin
Given IV
MOA:
Inhibit topoisomerase 2 w/c results in breakage
or inhibition of DNA strands and facilitating
accumulation of DNA breaks.
• USE:
• Testicular and prostrate carcinomas
• DOSE: 50-100mg/m2 for 5 days.

42. PACLITAXEL:
• Taxanes.
• MOA: binds to β tubulin subunit of microtubule ( diff
from vinca)→ promote microtubule polymerization,
inhibit depolymerization→ arrested in G2 and M
phases.
• USE: ovarian and breast cancer
• IV 75mg/m2 over 3 hrs infusion
• ADR: neutropenia
• Thrombocytopenia
• Peripheral neuropathy
• Hypersensitivity ( give dexa and H1 antagonist)

43. ANTIBIOTICS
• ADRIAMYCIN( DOXORUBICIN ,
DAUNORUBICIN)
• Anthracycline antibiotics
• MOA: cause DNA damage by intercalation into
DNA → intercalation interferes with action of
topoisomerase 2 resulting in blockade of
synthesis of DNA and RNA.
• Intracellular formation of free radicals also
cause DNA damage.

44. • Given IV
• Doxorubicin dose 75mg/m2 repeated after 21
days.
• USE
• Hodgkins lymphoma
• Myeloma
• Sarcoma
• Breast, endometrial, ovarian
• Lung
• Thyroid cancers

45. •
•
•
•
•
ADR:
Myelosuppression.
Cardiotoxicity ( arrthymia , abnormal ECG)
Brief not cause serious problem.
Dextrazoxane given for it b/c inhibitor of iron
mediated free radical formation.
• Liposomal formulation less cardiotoxic.

46. BLEOMYCIN:
• Glycopeptide mixture
• MOA: binds to DNA cause single strand and
double strand DNA breaks following free
radical formation and inhibition of DNA
synthesis.
• Cell cycle specific
• Active in G2 phase

47. •
•
•
•
•
•
•
DOSE
IV or IM or SC weekly 10-30units/m2
USE:
Hodgkins lymphoma
Head + neck cancer
Squamous cell cancer of cervix
Testicular cancer.

48. •
•
•
•
ADR:
Pulmonary dysfunction ( fibrosis , pneumonia)
Dose limiting
Mucocutaneous reaction ( alopecia,
hyperkeratosis)
• Hypersensitivity reactions common.

49. OTHER ANTI-CANCER AGENTS:
• L-ASPARGINASE:
• Is an enzyme used to treat acute lymphocytic leukemia
of childhood.
• MOA:
• Hydrolyzes asparagine w/c is required for growth of
tumor cell.
• Inhibits asparagine → drug shuts off protein + nucleic
acid synthesis.
• DOSE: 6000-10,000 IV every 3rd day for 3-4 weeks.
• ADR: hypersensitivity, pancreatitis.

50. PROTEIN TYROSINE KINASE INHIBITOR
• IMATINIB:
• MOA: is specific anticancer drug acts on
specific oncogene.
• Inhibits tyrosine kinase activity of protein
product of B cr-Abl oncogene that is expressed
in chronic myelogenous leukemia→ as result
proliferation of oncogene inhibited→
apoptosis results.

51. •
•
•
•
•
•
•
•
USE:
(1) CML
(2) GI stromal tumors ( C-kit tyrosine kinase)
ADR:
Diarrhea.
Fluid retention
DOSE:
400mg chronic dose QD orally.

52. GROWTH RECEPTOR INHIBITOR:
•
•
•
•
BEVACIZUMAB:
Is recombinant humanized monoclonal antibody.
MOA:
Inhibits natural protein vascular endothelial
growth factor (VEGF) that stimulates new blood
vessel formation.
• When VEGF is targeted and bound to
bevacizumab, no growth of blood vessels , tumor
do not get oxygen and nutrient for growth.

53. • USE:
• Metastatic colorectal cancer IV or infusion
5mg/kg once every 14 days.
• ADR:
• Myelosuppression
• Hypertension
• Stroke
• Angina
• CHF

54. INTERFERONS
• Effective in hairy cell leukemia

55. GONADAL HORMONE ANTAGONIST:
• TAMOXIFEN:
• MOA: acts by binding to estrogen receptors and
blocking estrogen dependent transcription in cells in G
phase.
• USE: breast cancer
• ADR: b/c it has agonist action in endometrium can
cause endometrial hyperplasia
• Nausea
• Vomitting
• Venous thrombosis
• Hot flushes.

56. • FLUTAMIDE:
• Anti-androgen
• MOA: bind to androgen receptor inhibit
androgen effects.
• USE: prostatic carcinoma.
• ADR: hot flushes
• Hepatic dysfunction
• Gynecomastia.

57. AROMATASE INHIBITOR:
• ANASTRAZOLE:
• Inhibit aromatase w/c catalyses conversion of
androstenedione (androgenic precursor) to
estrone ( estrogenic hormone)
• USE: advanced breast cancer
• ADR: hot flushes, bone and back pain
• Dyspnea
• DOSE: 1mg orally daily

58. MONOCLONAL ANTIBODIES:
• RITUXIMAB:
• Monoclonal antibody binds to surface protein in
non-hodgkin’s cell induces complement mediated
lysis , direct cytotoxicity and induction of
apoptosis
• USE: low grade lymphoma.
• ADR:
• Myelo suppression
• Hypersensitivity.

59. REGIMEN
•
•
•
•
•
MOPP → HODGKIN’S
Mechlorethamine
Vincristine
Procarbazine
Prednisolone.

60. •
•
•
•
•
ABVD
HODGKIN’S
Doxorubicin
Bleomycin
Vinblastine
Dacarbazine.

61. •
•
•
•
CMF BREAST
Cyclophosphamide
Methotrexate
5FU

62. •
•
•
•
•
•
CHOP non hodgkin’s
Carcinoma stomach
Cyclophosphamide
Doxorubicin
Vincristine
Prednisolone.