Dosing of mesna to avoid urothelial toxicity from cyclophosphamide infusion

Cyclophosphamide is an alkylating agent used as chemotherapy to treat a range of conditions, most notably certain types of cancer. It has useful immunosuppressive effects but is also predictably quite toxic.

One of the metabolites of cyclophosphamide is a toxic aldehyde called acrolein. Acrolein collects in the bladder following administration of cyclophosphamide and is an extreme irritant, leading to the development of hemorrhagic cystitis and potentially bladder cancer. In order to mitigate the damage to the bladder from acrolein accumulation, cyclophosphamide is usually co-administered with 2-mercaptoethanesulphonic acid, more easily remembered as mesna. Following administration, mesna concentrates in the bladder and forms complexes with acrolein, which renders it non-toxic. Given that this is a direct physical interaction between the acrolein and mesna, repeated doses are necessary to ensure there is mesna available in the bladder until all the metabolites have been excreted.

The following case considers the treatment of a vasculitis patient for whom an intermittent dose of fortnightly cyclophosphamide is required.