Cyclophosphamide (Cytoxan). A review on relevant pharmacology and clinical uses.

Cyclophosphamide (Cytoxan; Cy) is an alkylating agent with cytotoxic and immunosuppressive activities. The parent compound is inactive in vitro and exerts its biologic activity through metabolites, mainly phosphoramide mustard generated by hepatic microsomal enzymes. The exact mode of cytotoxic and immunosuppressive action of Cy at cellular level is not completely understood. Myelosuppression, hemorrhagic cystitis, alopecia, and gonadal damage are the main toxic effects. Available data suggest that Cy has carcinogenic potential in humans. Cy is widely used for cancer chemotherapy. As an immunosuppressive agent, it is successfully used in certain nonmalignant diseases in which autoimmune phenomena are established or suspected in the pathogenesis of the disease. It is the drug of choice in Wegener's granulomatosis. Extensive efforts are being made to synthesize Cy analogues with greater selective cytotoxic and immunosuppressive activity. Ifosfamide, a Cy analogue, appears to possess similar cytotoxic activity with less myelosuppression. Further research will help in synthesizing a Cy analogue with specific pharmacologic activity and reduced or absent harmful effects.