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Hematology and oncology ` hematology and oncology—PhaRmacology Hematology and oncology ` hematology and oncology—PhaRmacology SectIon III 441

Alkylating agents
dRUg mechanISm clInIcal USe adVeRSe eFFectS
Busulfan Cross-links DNA. Used to ablate patient’s bone Severe myelosuppression (in
marrow before bone marrow almost all cases), pulmonary
transplantation. fibrosis, hyperpigmentation.
Cyclophosphamide, Cross-link DNA at guanine. Solid tumors, leukemia, Myelosuppression; SIADH;
ifosfamide Require bioactivation by liver. lymphomas, rheumatic Fanconi syndrome
A nitrogen mustard. disease (eg, SLE, (ifosfamide); hemorrhagic
granulomatosis with cystitis and bladder cancer,
polyangiitis). prevented with mesna
(sulfhydryl group of mesna
binds toxic metabolites) and
adequate hydration.
Nitrosoureas Require bioactivation. Brain tumors (including CNS toxicity (convulsions,
(eg, carmustine, Cross blood-brain barrier glioblastoma multiforme). dizziness, ataxia).
lomustine) Ž CNS. Cross-link DNA.
Procarbazine Cell cycle phase–nonspecific Hodgkin lymphoma, brain Bone marrow suppression,
alkylating agent, mechanism tumors. pulmonary toxicity,
unknown. Also a weak MAO leukemia, disulfiram-like
inhibitor. reaction, tyramine-induced
hypertensive crisis with
consumption of tyramine-rich
foods (eg, aged cheese, wine,
fava beans).

Microtubule inhibitors
dRUg mechanISm clInIcal USe adVeRSe eFFectS
Paclitaxel, other Hyperstabilize polymerized Ovarian and breast carcinomas. Myelosuppression, neuropathy,
taxanes microtubules in M phase so hypersensitivity.
that mitotic spindle cannot Taxes stabilize society.
break down (anaphase cannot
occur).
Vincristine, vinblastine Vinca alkaloids that bind Solid tumors, leukemias, Vincristine: neurotoxicity
β-tubulin and inhibit Hodgkin and non-Hodgkin (areflexia, peripheral neuritis),
its polymerization into lymphomas. constipation (including
microtubules Ž prevent paralytic ileus). Crisps the
mitotic spindle formation nerves.
(M-phase arrest). Vinblastine: bone marrow
suppression. Blasts the bone
marrow.

FAS1_2019_10-HemaOncol.indd 441 11/7/19 5:05 PM