Question
Cyclophosphamide.
Answer
Cyclophosphamide is an alkylating agent, cell-cycle-nonspecific.
MOA: a prodrug, activated by hepatic CYP450 to reactive alkylating metabolites that form covalent cross-links between DNA strands (classically between guanine bases), preventing strand separation during replication and causing lethal DNA damage.
Uses: lymphomas, leukemias, solid tumors (combination regimens), and — at lower, non-oncologic doses — as an immunosuppressant in severe autoimmune disease (lupus nephritis, vasculitis).
Adverse effects: bone marrow suppression, hemorrhagic cystitis (its activation pathway generates the toxic byproduct acrolein, excreted in urine and damaging the bladder mucosa — prevented by co-administered mesna, which binds and neutralizes acrolein), alopecia, gonadal toxicity/infertility, secondary malignancy risk with cumulative dosing.