Alkylating Agents

Question 1

general alkylating agent MOA

Answer 1

produce strong electrophiles through carbonium/ethyleneimonium intermediates; alkylate nucleophilic moieties in DNA; most commonly add to N7 guanine, also N1,N3 adenine, N3 cytosine, O6 guanine

Question 2

mechlorethamine class

Answer 2

alkylating agent, nitrogen mustard

Question 3

mechlorethamine TU

Answer 3

Hodgkin’s as part of MOPP; topically for cutaneous T-cell lymphoma

Question 4

mechlorethamine Tox

Answer 4

nausea, vomiting, myelosuppression

Question 5

cyclophosphamide and ifosfamide general

Answer 5

alkylating agent, nitrogen mustard;
produrgs must be converted by P450
can be taken orally

Question 6

cyclophosphamide TU

Answer 6

lymphocytic leukemia, non-Hodgkin lymphoma, breast, lung, ovarian
in combos CHOP, CMF, FAC, FEC, etc

Question 7

ifosfamid TU

Answer 7

sarcoma, testicular carcinoma

Question 8

cyclophosphamide/ifosfamide Tox

Answer 8

hemorrhagic cystitis!! = irritation in bladder bc toxic metabolite acrolein in urine (adequate hydration, MESNA (inactivator) help minimize problem)

also nausea, vomiting, myelosuppression

Question 9

carmustine, lomustine general

Answer 9

alkylating agents, nitrosureas

Question 10

carmustine, lomustine TU

Answer 10

meningeal leukemias, brain tumors (highly lipophilic, can cross BBB)

Question 11

carmustine, lomustine Tox

Answer 11

renal toxicity, pulmonary fibrosis

nausea, vomiting, myelosuppression

Question 12

dacarbazine general

Answer 12

alkylating agent, triazene; prodrug activated by cytochromes in liver; given IV

Question 13

dacarbazine TU

Answer 13

malignant melanoma; in ABVD combo for Hodgkins

Question 14

dacarbazine Tox

Answer 14

nausea, vomiting, myelosuppression, flu-like symptoms

Question 15

temozolomide general

Answer 15

alkylating agent, triazene; prodrug nonenzymatic conversion at physiological pH; give orally

Question 16

temozolomide TU

Answer 16

malignant glioma

Question 17

temozolomide Tox

Answer 17

nausea, vomiting, myelosuppression, flu like symptoms

Question 18

cisplatin general

Answer 18

alkylating agent, platinum analog; converted to active form by rxn with water; intra- and interstrand cross-links

Question 19

cisplatin TU

Answer 19

efficacy over wide range; testicular, ovarian, cervical, bladder, head and neck, lung

Question 20

cisplatin Tox

Answer 20

nephrotoxicity, ototoxicity, peripheral motor and sensory neuropathy
nausea, vomiting, mild-mod myelosuppression

Question 21

carboplatin general

Answer 21

alkylating agent, platinum analog

Question 22

carboplatin TU

Answer 22

ovarian

Question 23

carboplatin Tox

Answer 23

less toxic, less reactive

thrombocytopenia

Question 24

oxaliplatin general

Answer 24

alkylating agent, platinum analog

Question 25

oxaliplatin TU

Answer 25

in combo with 5-FU for gastric and colorectal

Question 26

oxaliplatin Tox

Answer 26

peripheral sensory neuropathy (cold-induced acute peripheral neuropathy)
neutropenia