Background: Intravesical Bacillus Calmette-Guérin (BCG) is now a standard treatment for Ta, T1 carcinoma and carcinoma in situ (CIS) of the urinary bladder. In Japan, however, only BCG Tokyo 172 strain is commercially available. We therefore designed a clinical study of PMCJ-9 (BCG Connaught strain) for obtaining approval from Japanese Ministry of Health, Labor and Welfare.
Methods: In the phase I-II study, PMCJ-9 40.5, 81 (standard dose overseas) or 121.5 mg in saline was instilled into the bladder of patients with Ta, T1 or CIS once weekly for 8 weeks. The recommended dose was decided and similarly administered in the late phase II study.
Results: In the phase I-II study, 49 patients were evaluable for efficacy. The complete response (CR) rates were 60.0% (9/15), 68.2% (15/22) and 75.0% (9/12) in the 40.5, 81 and 121.5 mg groups. The incidence of adverse drug reactions (ADRs) was similar in all groups, but four 121.5 mg group patients developed severe ADRs. Thus, 81 mg was the recommended dose for the late phase II study. In that study, 39 patients were evaluable, showing CR rates of 71.8% (28/39) overall and 61.5% (16/26) and 92.3% (12/13) for the Ta, T1 and CIS cases. The safety was assessed in 42 patients and three (7.1%) were discontinued owing to ADRs.
Conclusion: The recommended dose for the BCG Connaught strain was decided as 81 mg. PMCJ-9 administration at this dose level weekly for 8 weeks showed a clear antitumor effect and good safety profile against Ta, T1 and CIS transitional cell carcinoma of the bladder.