[Bladder neoplasms and cyclophosphamide. Apropos pf 3 cases amd review of the literature].
We report three new cases of bladder cancer occurring in patients treated by cyclophosphamide (Endoxan): two patients had Waldenström disease and were treated during 7.5 and 7 years respectively (total received dose of 220 and 190 g respectively). The third patient was treated for autoimmune erythroblastopenia and the bladder cancer occurred 5 years after treatment by cyclophosphamide (39 g during 3.3 years). Bladder 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 tumor of 7 years. No other risk factor has been identified (tobacco, age, sex, hemorrhagic cystitis). The relative risk of bladder cancer is estimated between 7 and 9, and seems proportional to the cumulative dose of cyclophosphamide. The first hypothesis to explain bladder cancer occurrence is a carcinogenic effect of one of the cyclophosphamide metabolites, acrolein, but the immunosuppressive effect of cyclophosphamide may play a role. The risk of secondary bladder cancer implies to limit the use of cyclophosphamide, particularly in non malignant disease, and to closely watch the patient especially by way of annual cystoscopy.
Alexandre
J
J
Service d'hématologie, Hôtel-Dieu de Paris, France.
Lévy
V
V
Hunault
M
M
Bazarbachi
A
A
Delmer
A
A
Rio
B
B
Zittoun
R
R
D000368:Aged; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D003556:Cystitis / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006417:Hematuria / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D012010:Red-Cell Aplasia, Pure / Q000188:drug therapy; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy
D003520:Cyclophosphamide