BLADDER-CANCER AND CYCLOPHOSPHAMIDE - 3 C ASES AND A REVIEW OF THE LITERATURE

We report three new cases of bladder cancer occurring in patients trea ted by cyclophosphamide (Endoxan(R)): two patients had Waldenstrom dis ease and were treated during 7.5 and 7 years respectively (total recei ved dose of 220 and 190 g respectively). The third patient was treated for autoimmune erythroblastopenia and the bladder cancer occured 5 ye ars after treatment by cyclophosphamide (39 g during 3.3 years). Bladd er cancers after cyclophosphamide treatment are generally transitional cell carcinomas. They are observed after an oral treatment, generally given for more than one year. A cumulative dose of more than 20 g is the principal risk factor with a median interval from treatment to tum or of 7 years. No other risk factor has been identified (tobacco, age, sex, hemorragic cystitis). The relative risk of bladder cancer is est imated between 7 and 9, and seems proportional to the cumulative dose of cyclophosphamide. The first hypothesis to explain bladder cancer oc currence is a carcinogenic effect of one of the cyclophosphamide metab olites, acrolein, but the immunosuppresive effect of cyclophosphamide may play a role. The risk of secondary bladder cancer implies to limit the use of cyclophosphamide, particulary in non malignant disease, an d to closely watch the patient especially by way of annual cystoscopy.