RESUMEN
Sequential immuno-chemotherapy using bacillus Calmette-Guerin [BCG] and epirubicin has been found to be as effective as and less toxic than BCG alone in recurrence prophylaxis of superficial bladder tumors. Some investigators speculated that: if intravesical chemotherapy is instilled before immunotherapy it will produce inflammation and denudation of the mucosa so that the submucosa will be ready for a potentiated effect of the immunotherapy. To test this hypothesis we conducted this study. Between Jan. 1993 and July 1999 a prospective randomized trial was performed on 159 patients who underwent transurethral resection [[TURBT] of bladder transitional cell carcinoma [stages pTa and pTl]. Following TURBT, patients were randomly allocated to 2 treatment arms. Patients in arm I [78] received weekly doses of 150 mg BCG alternating with 50 mg epirubicin for 6 weeks. Maintenance was carried out by a monthly course of the same doses of BCG alternating with epirubicin for 10 months. Patients in arm II [81] received thy same protocol, but with a reversed order with epirubicin being used initially. 154 patients; 108 men and 36 women, mean age 59 years, were evaluable. 5 patients were excluded in view of severe side effects [3 in arm 1 and 2 in arm II]. Follow up ranged from 12 to 74 months [mean 38 +/- 16.9]. Recurrence rate was] comparable in the 2 arms: 11/75 [14.7%] and 13/79 [16.5%], respectively. Recurrence rate per 12 patient months was again; comparable: 0.08 and 0.09, respectively. Interval to first recurrence and progression rate were also comparable. Toxicity developed in 29% and 26.6% of patients, respectively [p > 0.05]. Both treatment policies were comparable in terms of efficacy and loxicity