Cyclophosphamide

Cyclophosphamide prevents cell division by cross-linking DNA strands. Cyclophos-phamide is activated to phosphoramide mustard and acrolein. Acrolein, which has no tumor activity, causes hemorrhagic cystitis of the bladder. The pharmacokinetics of cyclophosphamide are best described by a two-compartment model, with a terminal half-life that ranges from 4 to 10 hours. Approximately 15% of the dose is excreted unchanged by the kidney. Cyclophosphamide has shown clinical activity in numerous types of cancer, ranging from leukemias to lymphomas to breast and ovarian cancer. Whether the drug is administered orally or IV, patients need to be counseled on the importance of good hydration and frequent voiding to prevent hemorrhagic cystitis. Nausea and vomiting may occur 12 hours after administration, so patients need to have antiemetics available after the acute treatment period. Other side effects include myelosuppression, alopecia, SIADH (usually with doses greater than 50 mg/kg), secondary malignancies (e.g., bladder cancers and acute leukemias), and infertility issues.

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