Alkylating Agents

Question 1

Mechlorethamine

Answer 1

MOA: alkylating agent
USES: Hodgkin’s Disease, T-cell lymphoma
TOXICITY: myelosuppression

Question 2

Cyclophosphamide

Answer 2

MOA: prodrug converted to active alkylating metabolite by CP450
USES: broad spectrum, ALL/CLL, non-Hodgkin’s lymphoma, breast, lung, ovarian cancers
Toxicity: Hemorrhagic cystitis (acrolein metabolite-give MESNA)

Question 3

Ifosfamide

Answer 3

MOA: prodrug converted to active alkylating metabolite by CP450
USES: sarcoma and testicular cancer
Toxicity: nausea, vomit, myelosuppression

Question 4

Carmustine and Lomustine

Answer 4

MOA: alkylating nitrosureas
USES: highly lipophilic, cross BBB, brain tumors
Toxicity: profound myelosuppression, renal toxicity, pulmonary fibrosis

Question 5

Dacarbazine

Answer 5

MOA: prodrug converted by cytochromes in liver, IV administer
USES: part of ABVD, Hodgkin’s disease, malignant melanoma
Toxicity: myelosuppression, flu-like symptoms (fever, fatigue)

Question 6

Temozolomide

Answer 6

MOA: nonenzymatic conversion at normal pH, good bioavailability = taken orally
USES: malignant gliomas, in combo with radiation
Toxicity: myelosuppression, flu-like symptoms

Question 7

Cisplatin

Answer 7

MOA: alkylating agent by covalently bind to nucleophilic sites on DNA (different from other alkylating agents), react with water to become + charge, hydrated intermediate (instead of carbonium ion intermediate) form cross-links
USES: head/neck, lung carcinoma, testicular, ovarian, cervical, bladder cancers
Toxicity: nephrotoxicity, ototoxicity, peripheral motor and sensory neuropathy

Question 8

Carboplatin

Answer 8

MOA: same as cisplatin
USES: ovarian cancer
Toxicity: myelosuppression

Question 9

Oxaliplatin

Answer 9

MOA: same as cisplatin
USES: gastric and colorectal cancer
Toxicity: peripheral sensory neuropathy, cold-induced acute peripheral neuropathy