Bacillus Calmette-Guerin With or Without Interferon α-2b and Megadose Versus Recommended Daily Allowance Vitamins During Induction and Maintenance Intravesical Treatment of Nonmuscle Invasive Bladder Cancer

Purpose: In a multicenter, prospectively randomized study we evaluated bacillus Calmette-Guerin alone vs bacillus Calmette-Guerin plus interferon alpha-2b and megadose vitamins vs recommended daily allowance vitamins during induction and maintenance intravesical therapy in the treatment of nonmuscle invasive bladder cancer. Materials and Methods: Patients who were bacillus Calmette-Guerin naive with carcinoma in situ, Ta or T1 urothelial cancer were randomized to receive intravesical bacillus Calmette-Guerin or bacillus Calmette-Guerin plus interferon alpha-2b. Patients were further randomized to receive a recommended daily allowance or megadose vitamin preparation. Induction bacillus Calmette-Guerin treatment was given weekly for 6 weeks, and patients who were recurrence-free received maintenance treatment at 4, 7, 13, 19, 25 and 37 months. Patients were followed with quarterly cystoscopy for 2 years, then semiannually through year 4 and then annually. The primary end point was biopsy confirmed tumor recurrence or positive cytology. Results: A total of 670 patients were accrued and randomized. At 24-month median followup recurrence-free survival was similar in all groups with 63% in the bacillus Calmette-Guerin with recommended daily allowance vitamins group, 59% in bacillus Calmette-Guerin with megadose vitamins, 55% in bacillus Calmette-Guerin/interferon alpha-2b with recommended daily allowance vitamins and 61% in bacillus Calmette-Guerin/interferon alpha-2b with megadose vitamins (p >0.05). The addition of interferon alpha-2b was associated with a more frequent incidence of fever (11% vs 5%) and constitutional symptoms (18% vs 11%) vs bacillus Calmette-Guerin alone (p <0.05). Conclusions: Interferon alpha-2b added to bacillus Calmette-Guerin induction and maintenance intravesical therapy did not decrease tumor recurrence in bacillus Calmette-Guerin naive cases, but was associated with increased fever and constitutional symptoms. No difference in time to recurrence was present in patients receiving recommended daily allowance vs high dose vitamins.