Cancer Chemotherapy

Question 1

What is mechanism of alkylating agents?

Answer 1

Blocks DNA replication and transcription

Question 2

What are the cytotoxic actions of alkylating agents?

Answer 2

Proliferative dependent (except nitrosoureas)

Mainly affect G1 and S phases

Question 3

How do cells gain resistance to alkylating agents?

Answer 3

Decreased permeability or uptake; increased nucleophiles or repair

Question 4

What is Na-2-Mercaptoethanesulfonate

Answer 4

Used to decrease hemorrhagic cystitis produced by acrolein

Reacts with acrolein in urine to detoxify and prevent binding to bladder wall

Question 5

What are the four alkylating agents?

Answer 5

Mechlorethamine

Cyclophosphamide

Chlorambucil

Bendamustine

Question 6

What is unique about mechlorethamine?

Answer 6

It is not excreted

Question 7

What is mechlorethamine used for?

Answer 7

Hodgkins disease

Question 8

How is cyclophosphamide activated?

Answer 8

Activated by cytochrome P450s to active metabolites

Question 9

What are the unique toxicities of cyclophosphamide?

Answer 9

Hemorrhagic cystitis

SIADH

Question 10

What is Chlorambucil used for?

Answer 10

Chronic lymphocytic leukemia

Question 11

What is the unique toxicity for chlorambucil?

Answer 11

Hepatotoxicity

Question 12

What is the MoA of drugs containing platinum?

Answer 12

Binds to guanine in DNA; forms intrastrand crosslinks

Binds extensively to protein

Question 13

What are the dose-limiting toxicities of platinum drugs?

Answer 13

Nephrotoxicity

Peripheral neuropathy

Ototoxicity

Question 14

What are the anthracyclines and their MoA?

Answer 14

Doxorubicin and Daunorubicin

Tight binding between DNA base pairs

Blocks topoisomerase II

Question 15

What is the unique toxicity of anthracyclines?

Answer 15

Cardiotoxicity

Can be prevented by dexrazoxane

Question 16

What are the uses for anthracyclines?

Answer 16

Breast cancer

Sarcoma

MOPP-resistance Hodgkin’s

Carcinomas

Question 17

What is the MoA of mitoxantrone?

Answer 17

Binds to DNA to produce drug-DNA-topoisomerase II complexes

Lower incidence of cardiotoxicity

Question 18

What are the epipodophyllotoxins and their MoA?

Answer 18

Etoposide and Tenopside

Forms a ternary complex with DNa-topoisomerase

Kills in S and G2 phases

Question 19

What are the uses of epipodophyllotoxins?

Answer 19

Tisticular tumors

Small-cell lung cancer

Question 20

What is the MoA of Captothecin analogs?

Answer 20

Inhibitors of topoisomerase I

CCS: Act in S phase

Question 21

What are Bleomycins?

Answer 21

Combination of several structurally related antibiotics

Most active in G2 phase

Question 22

What are the unique toxicities of Bleomycins?

Answer 22

Pulmonaryy gibrosis and pneumonitis

Question 23

What are the uses of bleomycins?

Answer 23

Advanced testicular carcinoma

Lymphomas in combination therapy

Question 24

What is the MoA of dactinomycin?

Answer 24

Interaction at purine-pyrimidne base pairs of DNA and intercalate between strands

Prevents DNA transcription

Question 25

What are the unique toxicities of dactinomycin?

Answer 25

Oral and GI ulceration Stomatitis

Question 26

What are the uses for dactinomycin?

Answer 26

Methotrexate-resistant choriocarcinoma Wilm's tumor Rhabdomyosarcoma

Question 27

What are antimetabolites?

Answer 27

Compounds that mimic endogenous biochemicals required for DNA, RNA synthesis or function of enzymes

Question 28

What is the function of methotrexate?

Answer 28

Inhibits dihydrofolate reductase Decreases DNA synthesis CCS- S phase

Question 29

What is Leucovorin used for?

Answer 29

Minimizes the toxid effects of folate depletion in normal cells