cyclofosfamide

Cyclofosfamide is an alternative spelling for cyclophosphamide, a nitrogen mustard alkylating agent used in chemotherapy and, in some regimens, in immunosuppressive therapy. It is a prodrug that requires metabolic activation in the liver to form active species that alkylate DNA, leading to cross-linking and inhibition of cell replication. The primary active metabolite is phosphoramide mustard, produced through hepatic processing of 4-hydroxycyclophosphamide and related intermediates.

Medical uses of cyclofosfamide include treatment of a wide range of malignancies, such as non-Hodgkin and Hodgkin lymphomas, leukemias, breast and ovarian cancers, and multiple myeloma, often as part of combination regimens. It is also used in autoimmune diseases in high-dose regimens and in conditioning protocols for bone marrow or stem cell transplantation. Dosing can be oral or intravenous and is tailored to disease, patient factors, and concurrent therapies.

Pharmacokinetics and metabolism: cyclophosphamide is administered systemically and activated by hepatic cytochrome P450 enzymes. The resulting metabolites are distributed widely and excreted primarily in the urine. The drug’s effects reflect alkylation of DNA and other cellular targets, which is more pronounced in rapidly dividing cells but can affect normal tissues as well.

Adverse effects and safety: common toxicities include myelosuppression, nausea, vomiting, mucositis, and alopecia. A notable complication is hemorrhagic cystitis from the metabolite acrolein, for which mesna is sometimes used as a uroprotective agent. Other risks include infertility, secondary malignancies, nephrotoxicity, hepatotoxicity, and teratogenicity. Caution is advised in pregnancy and in patients with renal or hepatic impairment. Monitoring of blood counts and organ function is standard during therapy.