Cancer Chemotherapy

Question 1

Criteria for combination therapy

Answer 1

Should have different MOA
Should have different toxicities
Minimal cross reaction
Should be effective when used alone

Question 2

Cyclophosphamide

Answer 2

CCNS
Alkylate nucleophilic bases on DNA which leads to DNA strand breakages, cross linkind and abnormal base pairing.

Class : nitrogen mustards= chlorambucil, mechlorethamine

P450 mediated bio transformation producing acrolein

GIT disturbance, myelosuppression , alopecia
Acrolein> hemorhagic cystitis > drink water and mesna
Cardiac toxicity, pulmonary toxicity and SIADH

Question 3

Leukemia, NHL, breast and ovarian, neuroblastoma, multiple myeloma

Answer 3

Cyclophosphamide

Question 4

Hodgkin lymphomas and NHL

Answer 4

Mechlorethamine: converts into cytotoxic products in the body
Toxicity: GIT disturb, myelosuppression , alopecia, sterility
Blisters

Question 5

Cisplastn, carboplastin, oxaliplastin. IV

Answer 5

Testicular ca, bladder,lung,ovary cs.
Oxaliplastin: colon cancer

HNN: hematotoxic, neurotoxic, nephrotoxic (use mannitol wd forced hydration)
Tinnitus and hearing loss (CISPLASTIN)

Question 6

Procarbazine

Answer 6

Produces H2O2 causes strand scission
Hepatic metabolism
Enter CNS

Disulfuram like reaction
Inhibits liver enzymes monoamine oxidase
GIT, CNS, PERPHERAL neuropathy and skin reactions.

Question 7

Other alkylating agents

Answer 7

Busulfan: CML, Leukemia: adrenal insufficiency, pulmonary fibrosis, skin pigmentation
Carmistine/lomustine: adjunct in brain tumors
Dacarbazine: HL, : alopecia, skin rash, photo toxicity,flu like syndrome

Question 8

Anti metabolites CCS : S PHASE

Answer 8

Antagonists of folic acid: methotrexate
Purines: mercaptopurine , thioguanine
Pyrimidines: flurouracil,cytarabine, gemcitabine.

Question 9

Inhibit dihydrofolate reductase

Answer 9

Methotrexate so synthesis of thymidylate is less.
Oran and IV
Hydration to prevent crystal formation in renal tubules

Chorionic ca, acute leukaemia,NHL,
Psoriasis, RA, ectopic pregnancy

Toxicity: bone marrow suppression, mucositis, (administer folinic acid). This is leucovorin rescue,
Long term use: hepatotoxic, pulmonary infiltrate and fibrosis

Question 10

Which anti metabolites are activated by HGPRTases to toxic nucleotides

Answer 10

Mercaptopurine and thioguanine = then they inhibit several enzymes involved in purine metabolism
Low oral: first pass metabolism.
Allopurinol and fubexostat inhibit xanthine oxidase

CML and AL

Cholestasis , hepatotoxic
Bone marrow suppression

Question 11

Flurouracil. IV

Answer 11

5FU>5dUMP + FUTP> thymidylate synthase inhibition
Thiamineless death
Inhibits DNA/RNA function

CNS
Toxicity: GI distress, myelosuppression, alopecia

Question 12

Pyrimidine antimetabolites

Answer 12

Kinases> AraCTP> inhibitor of DNA polymerase
Most specific for S phase

Gemcitabine: converted to diphosphate : inhibit ribonucleotide reductase - DNA synthesis
Gemcitabine triphosphate can be incroporated into DNA causing chain to terminate
Toxicity: primary myelosuppression, NEUTROPENIA, pulmonary toxicity

Question 13

Megaloblastic anemia

Answer 13

Hydroxyurea

Question 14

M phase specific that block formation of mitotic spindle by preventing assembly of tubulin dimers

Answer 14

Vinblastin, : GIT, Alopecia, bone marrow suppressuion
vincristine, : neurotoxic, areflexia, paralytic ileus, peripheral neuritis
vinorelbine:
NAPP

Biliary excretion

Question 15

Late S and early G2 phase

Answer 15

Etoposide: - topoisomerase 2
Teniposide
Reduce dose in kidney patients.

Question 16

Inhibit topoisomerase 1

Answer 16

Topotecan and isotecan: converted into SN 38 ( renal and bile/feces)
Low glucoronidation activity in UGT1A

Myelosuppression and diarrhoea

Question 17

Paclitaxel wnd docetaxel. IV

Answer 17

Prevent microtubule disassembly into monomers

Paclitaxel: neutropenia/ thrombocytopenia
Peripheral neuropathy hypersensitive
Docetaxel: neurotoxic and bone marrow suppression