Chemotherapy And Cytotoxic Drugs

Question 1

Cancer prevalence in m/f

Answer 1

M: prostate > lung > colon
F: breast > lung > colon

Question 2

Cancer deaths M/F

Answer 2

M: lung > colon > prostate
F: lung > breast > colon

Question 3

What kinds of tumors are most sensitive to cell cycle specific drugs?

Answer 3

Rapidly growing with growth fraction >70%, acute leukemia and high grade lymphomas

Question 4

What kinds of tumors are more affected by cell-cycle nonspecific drugs?

Answer 4

Cancer cells that are cycling or in the resting state (G0)

Abx (except bleomycin), alkylating agents, camptothecins at high concentrations

Question 5

Phases of Chemo tx of disseminated cancer

Answer 5

Induction: initial high dose
Consolidation: high dose for months
Maintenance: low dose for months/yrs

Question 6

Examples of alkylating agents

Answer 6

Cyclophosphamide

Cisplatin

Question 7

Alkylating agents MOA and resistance

Answer 7

Cyclophosphamide, Cisplatin
MOA: alkylate DNA at Guanine -> cross link of DNA -> can’t repair -> apoptosis
Resistance: inc DNA repair, dec transport

Question 8

Cyclophosphamide AE, dose limiting

Answer 8

Nitrogen mustard
AE: hemorrhagic cystitis
DL: myelosuppression

Question 9

Cisplatin AE, DL

Answer 9

Platinum analog
AE: ototoxic
DL: nephrotoxicity (hydration, mannitol preventioN)

Question 10

Examples of anti-metabolite drugs

Answer 10

MTX
5FU
6MP

Question 11

MOAs as analogs of antimetabolites

Answer 11

MTX - folic acid analog
6MP - purine analog
5FU - pyrmidine analog

Question 12

What is the most commonly used cytotoxic anti cancer agent

Answer 12

MTX

Question 13

MTX MOA, AE

Answer 13

MOA: prevents THF formation leading to interruption of DNA, RNA, protein synth
AE: myelosuppresion, GI,renal
Give with leucovorin to rescue normal cells

Question 14

6MP MOA, AE

Answer 14

MOA: metab by HGPRT -> TIMP replaces endogenous IMP, converted to t-dGMP and damages DNA
AE: myelosuppression that is worse with allopurinol

Question 15

5FU MOA, AE

Answer 15

MOA: 5-FUTP -> inhibits TS
AE: myelosuppresion

Question 16

Examples of vinca alkaloids, MOA

Answer 16

VinBlastine
VinCristine
MOA: binds to B tubular, blocks spindle formation, arrest at metaphase interferes with chromosome segregation -> death

Question 17

VinBlastine use and tox

Answer 17

Vinca alkaloid
Use: Breast, testicular
Tox: bone marrow suppression

Question 18

VinCristine use, tox

Answer 18

Use: childhood leukemia and tumors
Tox: neuritis, neuropathy, muscle weakness
Marrow sparing effect*

Question 19

Which drug is a taxane?

Answer 19

Paclitaxel

Question 20

Paclitaxel MOA, AE

Answer 20

MOA: binds to B tubule and prevents microtubule depolymerization
AE: myelosuppression and peripheral neuropathy

Question 21

Example of a epipodophyllotoxin

Answer 21

Etoposide

Question 22

Etoposide MOA, AE

Answer 22

MOA: blocks topoisomerase II
AE: myelosuppresion, alopecia

Question 23

Example of camptothecins

Answer 23

Irinotecan

Question 24

Irinotecan MOA, AE

Answer 24

MOA: inhibits topoisomerase I
AE: myelosuppression and diarrhea

Question 25

How does tumor resistance develop against vinca alkaloids, taxanes, epipodophyllotoxins, and camptothecins?

Answer 25

inc MDR1 gene expression

Question 26

Cytotoxic ABX and MOA

Answer 26

Doxorubicin
Bleomycin
MOA: intercalation insertion between base pairs

Question 27

Doxorubicin MOA, AE

Answer 27

MOA: intercalation, inhib topo II, generation of free radicals
AE: irreversible cardiomyopathy, also acute arrhythmias

Question 28

Bleomycin MOA, AE

Answer 28

MOA: intercalation, oxidation via bleomycin Fe II complex
DL: pulmonary fibrosis