Cyclophosphamide is contraindicated in patients with a history of transitional cell carcinoma

Abstract

Cyclophosphamide is a urotoxic agent that increases the incidence of malignant neoplasms of the urinary tract. The aim of this study was to evaluate the long-term impact of cyclophosphamide on patients with a history of superficial bladder cancer. Between July 1986 and January 1988, 58 consecutive patients with primary superficial transitional cell carcinoma of the bladder were included in this study. All patients had a transurethral R0 resection. Then 6 weekly intravesical instillations of 120 mg bacillus Calmette-Guérin (BCG) were performed. Until June 1987, 22 consecutive patients (group A) received an additional intravenous application of 700 mg/m² cyclophosphamide prior to the BCG immunotherapy, while from July 1987 36 patients were treated without cyclophosphamide. Survival was calculated using the Kaplan-Meier method and comparison of survival using the log rank test. Tumor staging, grading, and size were equally distributed in both groups. No significant difference could be observed regarding the 10-year overall survival rate (group A: 59%, group B: 58%), the 10-year tumor-specific survival rate (89 vs 94%), and the 10-year progression-free survival rate (85 vs 97%). There was a statistically significant deterioration of the 10-year recurrence-free survival rate in the cyclophosphamide group (44 vs 70%, log rank test: p<0.05). Whereas there were no recurrences in the upper urinary tract among the patients of group B, 2 of the 22 patients from group A developed cancer of the renal pelvis. In patients with a history of superficial bladder cancer, a single dose of cyclophosphamide poses a significantly increased risk of tumor recurrence in the lower and in the upper urinary tract as well.