Which agent in R-CHOP is most associated with hemorrhagic cystitis?

• A. Doxorubicin
• B. Rituximab
• C. Cyclophosphamide
• D. Vincristine

Answer: (C)

Hemorrhagic cystitis comes from a bladder-irritating metabolite produced by some chemotherapy drugs. In this regimen, the alkylating agent cyclophosphamide is metabolized to acrolein, which is excreted in the urine and can inflame the bladder lining, causing bleeding and irritation. That direct link to acrolein makes cyclophosphamide the one most associated with this toxicity. To prevent it, mesna is often given to bind acrolein in the urinary tract, and good hydration helps dilute and flush the bladder. If symptoms occur, adjustments in dosing or mesna support can be used. Other drugs in the combination have different toxicities—doxorubicin tends toward cardiotoxicity and mucositis, rituximab can cause infusion reactions and infections, and vincristine causes neurotoxicity—so they are not the classic culprits for hemorrhagic cystitis.