Phase B

Question 1

Methotrexate

Answer 1

Anti-neoplastic.

Can be used to treat choriocarcinoma (gestational trophoblastic neoplasm) with or without Leucovorin rescue

Interferes with Folate pathway, inhibiting DHFR, and preventing synthesis of Thymidine.

Also depletes folate stores, leading to decreased purine synthesis.

Question 2

Cell-Cycle Specific Agents

Answer 2

Fluorouracil, mercaptopurine, methotrexate, bleomycin, vincristine, vinblastine

Question 3

Cell-Cycle Non-Specific Agents

Answer 3

Cyclophosphamide, daunorubicin, doxorubicin, cisplatin, oxaliplatin

Question 4

Combination Chemotherapy

Answer 4

Prevention of resistance.

Use of cell cycle specific and cell cycle nonspecific drugs.

Additive or synergistic mechanisms of action by combinations of active agents or of an active and inactive agent.

Different (non-overlapping) toxicities (eg, myelosuppression)

Question 5

Nitrogen Mustards

Answer 5

Examples: Cyclophosphamide, Melphalan, Chlorambucil, Mechlorethamine.

MOA: Activated by hepatic CYPs, then cross-link DNA.

Can also lead to formation of Acrolein, a side-product that is injurious to the bladder (can be treated with MESNA).

Only useful if p53 is still present to halt replication Can be inhibited by Glutathione

Question 6

Intercalating Agents

Answer 6

Examples: Doxorubicin, Daunorubicin, Idarubicin, Bleomycin

Intercalate between base pairs of DNA, leading to insertion and deletion mutations.

Doxorubicin also leads to oxidative damage free radical formation interacting with iron.

This is cause for cardiac toxicity. Bleomycin is a strict intercalater

Question 7

Topoisomerase Inhibitors

Answer 7

Examples: Doxorubicin and Irinotecan

Doxorubicin: Topo II

Irinotecan: Topo I

Stabilize Topo-DNA bond, leading to inactive Topo bound to DNA

Question 8

Cisplatin and Oxaliplatin

Answer 8

Platinum containing anti-neoplastic drugs.

Oxaliplatin has a higher toxicity than Cisplatin.

Oxaliplatin can form both inter- and intra-strand DNA linkages, overcoming resistance to Cisplatin due to overcoming mismatch repair

Question 9

5-Fluorouracil

Answer 9

5-FU can be used in combination with methotrexate.

It directly inhibits thymidylate synthase.

It can also inhibit RNA processing and be incorporated into DNA

Question 10

Mercaptopurine and 6-Thioguanine

Answer 10

Purine analogs that inhibit purine synthesis.

HGPRT is needed to first convert 6-MP to Thio-IMP, which then inhibits the first step of purine synthesis by PRPP glutamyl transferase

Question 11

Vinblastine and Vincristine

Answer 11

MOA: Stabilize microtubules leading to inhibition of cell division.

Vinblastine “blasts” bone marrow

Vincristine is better for children, can lead to neuro-toxicity

Question 12

Letrozole

Answer 12

Used in breast cancer that is estrogen sensitive.

It blocks synthesis of estradiol in tumors