IMPROVING THE EFFICACY OF BCG IMMUNOTHERAPY BY DOSE REDUCTION

Several clinical trials have shown intravesical bacillus Calmette-Guer in (BCG) to be effective in the prophylaxis of papillary tumour recurr ences and in the therapy of bladder carcinoma in situ (CIS), as well a s in delaying progression to muscle invasion. Nevertheless, the optima l regimen of BCG therapy for superficial bladder cancer has still to b e defined. In a previous phase II trial, a low-dose regimen (BCG Paste ur strain, 75 mg) was able to achieve clinically significant response rates with a decrease in side-effects compared with other reported stu dies using standard-dose BCG. However, a phase III randomized trial - low dose versus standard dose (BCG Pasteur strain, 75 vs. 150 mg) - wa s considered necessary to clarify definitively the relationships betwe en dose, efficacy and toxicity. The results of the interim analysis of 183 patients (performed in 1993) have shown response rates to be bett er in patients submitted to a low-dose BCG regimen (p = 0.0009) and a significant decrease in most of the common side-effects (cystitis, fev er, haematuria; p < 0.05). Breaking down the results by stage, no diff erences in response rates were found in patients with stage TaM (70 vs . 62% in low-dose and standard-dose regimens, respectively, p = 0.5). In T1M and CIS stages, 82 and 0 (p = 0.07), and 64 and 0% (p = 0.0003) of patients were free of tumour following low-dose and standard-dose therapy, respectively. An additional 6-week course in patients who fai led the induction course retrieved additional responses in both groups . No differences in progression rates were observed. In conclusion, a low-dose regimen gives superior protection from recurrences with a dec rease in side-effects; an additional 6-week course can achieve further complete responses in patients who failed the induction course.