Which chemo agent is commonly associated with hemorrhagic cystitis?

• A. Methotrexate
• B. Etoposide
• C. Ifosfamide
• D. Carboplatin

Answer: (C)

Hemorrhagic cystitis is caused when a bladder-irritating metabolite is shed into the urine. Ifosfamide is well known for producing acrolein, a reactive metabolite that accumulates in the bladder and can inflame and bleed the bladder lining. Because of this risk, clinicians use Mesna to bind acrolein and give aggressive hydration to flush the bladder when ifosfamide (and cyclophosphamide, which can do this as well) is given. The other drugs listed have different toxicity profiles and are not commonly associated with hemorrhagic cystitis; methotrexate mainly causes mucositis and renal toxicity, etoposide can cause myelosuppression and secondary leukemias, and carboplatin tends toward myelosuppression and nephro-/neurotoxicity rather than bladder hemorrhage.