• 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
• ONCOGENE: mutant form of normal gene found
in naturally occuring tumors w/c when expressed
in non-cancerous cells cause them to behave like
PRINCIPLES OF CANCER
• Cause a lethal cytotoxic event or apoptosis in
cancer cell that can arrest tumor’s
• 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).
• 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
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.
• Mitotic phase ( cell
• VINCA ALKALOIDS
• DNA is replicated
• Synthesis of
enzymes needed for
• Rapidly dividing cells are generally more
sensitive to anticancer drugs whereas slowly
proliferating cells are less sensitive.
• G0 phase cell survive most agents.
• 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”
• Vinca alkaloids
• Effective for high growth fraction malignancies as
• 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
• Solid tumors + low + high growth fraction
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.
TREATMENT REGIMENS AND
• 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
• 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
• Combination drug chemotherapy is more
successful than single drug treatment
• COMBINATION OF DRUGS:
• Cytotoxic agents with different toxicities,
different molecular sites and MOA are
• Better effects due to potentiated effects.
• If similar toxicity drugs combined dose should
ADVANTAGES OF COMBINATION
• 1. provide maximal cell killing within range of
• 2. are effective against broader range of cell
lines in heterogenous tumor population.
• 3. may delay or prevent development of
resistant cell lines.
Narrow therapeutic index
Vomitting ( anti-emetic)
Bone marrow suppression.
Pulmonary fibrosis( bleomycin)
• Megaloblastic anemia caused by methotrexate
can be overcome by FOLINIC ACID (
• Neutropenia ( human granulocyte colony
stimulating factor) FILGRASTIM can be given.
• 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.
• 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
• ADR: vesicant action.
• Converted to 4-hydroxycyclophosph
CyP2B enzyme → in tumor cell cleav
phosphoramide and acrolein
• Phosphoramide mustard is responsib
• ADR :
• Acrolein causes hemorrhagic cystitis
• Ample fluid should be taken
• MESNA ( mercaptoethane sulfonate)
cystitis traps acrolein.
1. malignant lymphomas.
2. Hodgkins disease.
4. breast and ovarian cancer.
IV dose 50mg/kg divided dose over 2-5 days.
Orally 1-5 mg/kg for initial and maintenace
Useful for brain tumor
Metastatic brain tumor
Hodgkins and non hodgkins lymphoma
DOSE: 150-200mg/m2 given IV for 6 weeks as
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
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.
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
• Is reactive agent that forms hydrogen peroxide
w/c generates free radicals that cause DNA
• KINETICS: orally active penetrates tissues
• USE: component regimen for Hodgkins
• ADR: myelosuppressant
• GI irritation
• CCS drugs acting primarily in S phase of cell cycle.
• 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.
• 1. drug accumulation decreased.
• 2. changes in drug sensitivity or activity of
• 3. decrease formation of polyglutamate.
• IV and oral good distribution except CNS.
• Not metabolized clearance depends on renal function.
• Adequate hydration needed to prevent crystallization
in renal tubules.
4 cutaneous T cell lymphoma.
5 breast cancer
DOSE: 15-30mg/day orally or IV 5 days.
Meningiocarcinoma given IT.
2.bone marrow suppression.
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)
• 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.
• Treatment of bladder, breast, colon, head and
neck, liver and ovarian cancers.
• 12mg/kg IV for 4 days.
• 6 mg/kg on alternate days for 4 doses.
Mercaptopurine in presence of hypoxanthine guanine
phosphoribosyl transferase → thioinosine mono
phosphate (TIMP) → inhibits purine synthesis.
• TIMP → thiguanine mono phosphate and thioguanine
• Cytotoxic effect of mercaptopurine is result of
incorporation of these nucleotides into DNA.
Semi-synthetic derivatives of podophyllotoxin
Inhibit topoisomerase 2 w/c results in breakage
or inhibition of DNA strands and facilitating
accumulation of DNA breaks.
• Testicular and prostrate carcinomas
• DOSE: 50-100mg/m2 for 5 days.
• MOA: binds to β tubulin subunit of microtubule ( diff
from vinca)→ promote microtubule polymerization,
inhibit depolymerization→ arrested in G2 and M
• USE: ovarian and breast cancer
• IV 75mg/m2 over 3 hrs infusion
• ADR: neutropenia
• Peripheral neuropathy
• Hypersensitivity ( give dexa and H1 antagonist)
• ADRIAMYCIN( DOXORUBICIN ,
• 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.
• Given IV
• Doxorubicin dose 75mg/m2 repeated after 21
• Hodgkins lymphoma
• Breast, endometrial, ovarian
• Thyroid cancers
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.
• Glycopeptide mixture
• MOA: binds to DNA cause single strand and
double strand DNA breaks following free
radical formation and inhibition of DNA
• Cell cycle specific
• Active in G2 phase
IV or IM or SC weekly 10-30units/m2
Head + neck cancer
Squamous cell cancer of cervix
OTHER ANTI-CANCER AGENTS:
• Is an enzyme used to treat acute lymphocytic leukemia
• Hydrolyzes asparagine w/c is required for growth of
• Inhibits asparagine → drug shuts off protein + nucleic
• DOSE: 6000-10,000 IV every 3rd day for 3-4 weeks.
• ADR: hypersensitivity, pancreatitis.
PROTEIN TYROSINE KINASE INHIBITOR
• MOA: is specific anticancer drug acts on
• 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→
GROWTH RECEPTOR INHIBITOR:
Is recombinant humanized monoclonal antibody.
Inhibits natural protein vascular endothelial
growth factor (VEGF) that stimulates new blood
• When VEGF is targeted and bound to
bevacizumab, no growth of blood vessels , tumor
do not get oxygen and nutrient for growth.
• Metastatic colorectal cancer IV or infusion
5mg/kg once every 14 days.
• Effective in hairy cell leukemia
GONADAL HORMONE ANTAGONIST:
• MOA: acts by binding to estrogen receptors and
blocking estrogen dependent transcription in cells in G
• USE: breast cancer
• ADR: b/c it has agonist action in endometrium can
cause endometrial hyperplasia
• Venous thrombosis
• Hot flushes.
• 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
• DOSE: 1mg orally daily
• Monoclonal antibody binds to surface protein in
non-hodgkin’s cell induces complement mediated
lysis , direct cytotoxicity and induction of
• USE: low grade lymphoma.
• Myelo suppression