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Cyclophosphamide Treatment Tied to Urinary Tract Cancer

Cumulative cyclophosphamide dose and oral administration identified as independent predictors

WEDNESDAY, March 9 (HealthDay News) -- Patients with systemic necrotizing vasculitides (SNV) treated with cyclophosphamide (CYC) have a five-fold higher risk of developing urinary tract cancer (UTC), according to a study published online Feb. 17 in Arthritis & Rheumatism.

Guillaume Le Guenno, M.D., from the Assistance Publique-Hôpitaux de Paris, and colleagues assessed the incidence and predictors of hemorrhagic cystitis (HC) and/or UTC in SNV patients treated with CYC. Data were collected from 805 patients in the French Vasculitis Study Group database diagnosed with Wegener's granulomatosis (WG), microscopic polyangiitis, Churg-Strauss syndrome or polyarteritis nodosa who were treated with CYC and followed up for an average of 5.3 years. Standardized incidence ratios (SIR) were calculated to compare observed UTC incidence to that expected in the general population. The relationship of UTC and/or HC with variables including CYC dose and administration route was studied in a subgroup of 467 patients with detailed information on CYC exposure.

The investigators identified 22 cases of HC and seven cases of UTC in 27 patients. SIR for UTC and WG was 5.00 and 5.96, respectively. Cumulative CYC dose (hazard ratio [HR] for 10-gram increments, 1.09), history of ever receiving oral CYC therapy (HR, 5.50) and WG (HR, 2.96) were identified as independent predictors of UTC and/or HC. Other significant predictors of UTC were tobacco smoking (HR, 8.20) and a prior HC episode (HR, 5.20).

"The results of this study on urotoxic adverse events in CYC-treated SNV patients strengthen the link with cumulative CYC exposure and highlight oral CYC and perhaps also WG as additional independent risk factors," the authors write.

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