INTRAVESICAL INSTILLATION OF EPIRUBICIN, BACILLUS CALMETTE-GUERIN AND BACILLUS CALMETTE-GUERIN PLUS ISONIAZID FOR INTERMEDIATE AND HIGH RISK TA, T1 PAPILLARY CARCINOMA OF THE BLADDER: A EUROPEAN ORGANIZATION FOR RESEARCH AND TREATMENT OF CANCER GENITO-URINARY GROUP RANDOMIZED PHASE III TRIAL

PURPOSE: After transurethral resection, we compared the efficacy and side effects of weekly intravesical instillations of epirubicin, bacillus Calmette-Guerin (BCG), and BCG plus isoniazid during a 6-week interval followed by 3 weekly maintenance instillations at months 3, 6, 12, 18, 24, 30 and 36 in patients with intermediate and high risk Ta, T1 bladder cancer. MATERIALS AND METHODS: A total of 957 patients were randomized at 44 institutions in a phase III multicenter trial. RESULTS: The time to first recurrence was significantly longer in patients treated with BCG and BCG plus isoniazid compared to epirubicin (p = 0.0001) but there was no difference between the 2 BCG regimens (p = 0.27). Progression to muscle invasive cancer was rare (5%) and did not differ significantly among the 3 arms (p = 0.12). Drug induced cystitis was observed in 31% of the patients treated with epirubicin, 42% BCG and 45% BCG plus isoniazid. Systemic side effects, such as fever and malaise, were not observed in patients treated with epirubicin, but were noted in 31% BCG and 36% BCG plus isoniazid. CONCLUSIONS: Intravesical BCG with or without isoniazid provokes more side effects than epirubicin. Prophylactic isoniazid does not reduce the side effects of BCG, while BCG with or without isoniazid prolongs the time to first recurrence compared to epirubicin. Further followup is required before long-term conclusions can be made for progression-to-muscle invasive disease and survival.