Alkylating agents

Question 1

busulfan

Answer 1

Class: alkylating agents

MOA: Cross-links DNA.

Clinical use: Used to ablate patient’s bone
marrow before bone marrow
transplantation.

Adverse effects: Severe myelosuppression (in
almost all cases), pulmonary
fibrosis, hyperpigmentation

Question 2

Cyclophosphamide,

ifosfamide

Answer 2

Class: alkylating agents

MOA: Cross-link DNA at guanine.
Require bioactivation by liver.
A nitrogen mustard

Clinical use: Solid tumors, leukemia,
lymphomas, rheumatic
disease (eg, SLE,
granulomatosis with
polyangiitis).

Adverse effects: Myelosuppression; SIADH;
Fanconi syndrome
(ifosfamide); hemorrhagic
cystitis and bladder cancer,
prevented with mesna
(sulfhydryl group of mesna
binds toxic metabolites) and
adequate hydration

Question 3

Nitrosoureas
(eg, carmustine,
lomustine)

Answer 3

Class: alkylating agents

MOA: Require bioactivation.
Cross blood-brain barrier
–> CNS. Cross-link DNA

Clinical use: Brain tumors (including
glioblastoma multiforme

Adverse effects: CNS toxicity (convulsions,
dizziness, ataxia).

Question 4

Procarbazine

Answer 4

Class: alkylating agents

MOA: Cell cycle phase–nonspecific
alkylating agent, mechanism
not yet defined.

Clinical use: Hodgkin lymphoma, brain
tumors.

Adverse effects: Bone marrow suppression,
pulmonary toxicity, leukemia,
disulfiram-like reaction.