Ifosfamide, used in Ewing sarcoma protocols, produces haemorrhagic cystitis as its characteristic urothelial toxicity. This complication is prevented by co-administration of mesna, which acts by:

• A Alkalinising urine to reduce epithelial uptake of chloroacetaldehyde
• B Inhibiting renal tubular secretion of ifosfamide metabolites
• C Neutralising free radicals generated in bladder smooth muscle
• D Binding acrolein in the urine to form an inert thioether ✓

Explanation

Acrolein, a urinary metabolite of oxazaphosphorines such as ifosfamide and cyclophosphamide, is directly toxic to bladder transitional epithelium. Mesna is a sulphydryl compound excreted in urine where it conjugates with acrolein, rendering it inert before it contacts the urothelium. It does not alter systemic antitumour activity. Alkalinisation is not the mechanism, and mesna does not address ifosfamide-induced encephalopathy, which is attributed to chloroacetaldehyde.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

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Written and medically reviewed by the StethoPrep medical team.