Which cytotoxic drug is most likely associated with urothelial toxicity requiring Mesna during treatment?

• A. Cisplatin
• B. Methotrexate
• C. Cyclophosphamide
• D. Doxorubicin

Answer: (C)

Urothelial toxicity with Mesna protection occurs when a drug metabolizes to acrolein, a bladder-irritating compound. Mesna supplies a thiol group that binds acrolein in the urine, forming non-toxic complexes and preventing hemorrhagic cystitis. Cyclophosphamide is a classic example where Mesna is routinely given to prevent this urothelial injury (and ifosfamide uses Mesna as well, though not in this list). The other drugs listed have different toxicity profiles—cisplatin mainly causes nephrotoxicity, methotrexate can cause mucositis and myelosuppression, and doxorubicin is notable for cardiotoxicity and myelosuppression rather than bladder irritation requiring Mesna.