Mesna cyclophosphamide therapy

In 155 patients with Wegener s granulomatosis, of whom 142 took daily oral cyclophosphamide, the most frequent long-term cyclophosphamide-related adverse effects were cystitis despite mesna therapy (12%) and myelodysplasia (8%) (25). Patients who took a cumulative dose of over 100 g had a two-fold greater risk of cystitis and/or myelodysplasia than patients who took under 100 g. The authors emphasized that cyclophosphamide therapy should be as short as possible, with mesna and close surveillance in order to reduce treatment-associated morbidity. 

Direct contact of the bladder epithelium with the catabolites acrolein and 4-hydroxy-cyclophosphamide is responsible for the hemorrhagic cystitis that can be a consequence of therapy with cyclophosphamide [78]. Aggressive hydration provides prophylaxis against this toxicity to the efferent urinary tract [79]. The sulfhydryl compound mesna has also demonstrated uroprotec-tive ability during therapy with cyclophosphamide [80]. Although hemorrhagic cystitis is a dose-related toxicity, chronic low doses of orally administered cyclophosphamide are also associated with development of this adverse event [81]. 

Treatment is largely supportive. Cyclophosphamide is adsorbed to activated charcoal and charcoal should be used for substantial, recent ingestions. Patients may require aggressive fluid support. Standard supportive therapies, such as vasopressors, should be utilized as clinically indicated. Patients may require prolonged observation due to the delay in the development of adverse effects. Antibiotics may be needed due to development of immunosuppression. MESNA has been used for management of cyclophosphamide-induced hemorrhagic cystitis. 

Drug therapy may also cause renal insufficiency due to lower urinary tract obstruction. Ureteral obstruction can be caused by calculi or retroperitoneal fibrosis. Bladder dysfunction with urinary outflow obstruction can result, particularly in males with prostatic hypertrophy, from anticholinergic drugs including tricyclic antidepressants and disopyramide. Bladder outlet and ureteral obstruction may result from bladder fibrosis following hemorrhagic cystitis with cyclophosphamide or ifosfamide therapy. Concurrent treatment with mesna can prevent cystitis and this complication. 

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