Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with...

We report the second interim analysis of data from a randomized prospective trial comparing the prophylactic effect of 15 courses of 50 mg. doxorubicin, 50 mg. thiotepa or 150 mg. bacillus Calmette-Guerin instilled intravesically against recurrences and progression of superficial transitional cell bladder cancer. Of 202 enrolled patients 176 currently are evaluable with a mean follow-up of 3 years (range 3 to 97 months). The number of patients with recurrences was significantly lower in the bacillus Calmette-Guerin arm (9 of 67) compared to the doxorubicin (23 of 53, p equals 0.002) and thiotepa (20 of 56, p equals 0.003) arms. The over-all recurrence index per 100 patient-months also was lower for the bacillus Calmette-Guerin versus the thiotepa and doxorubicin groups (0.53 versus 1.55 and 1.7, respectively). Bacillus Calmette-Guerin also was superior in preventing recurrences and progression of high risk tumors, that is stage T1, grade 3 or multiple growths, associated or not with carcinoma in situ. In the stage T1 category 19 of 32 (60%) tumors recurred under treatment with doxorubicin, 11 of 33 (33%) with thiotepa and 6 of 49 (12%) with bacillus Calmette-Guerin. Toxicity to intravesical bacillus Calmette-Guerin was higher compared to the other drugs but it was not limiting: bladder irritability and malaise occurred in 42% of the patients, granulomatous cystitis in 16.4% and bladder contraction in 1.4% (1 of 64). The latter complication occurred in a patient whose stage T1m grade 2 tumors had recurred 3 times, who underwent 3 transurethral bladder resections within 15 months and who had received thiotepa for 4 months after having been removed from the study 11 months after entry. Three patients in the doxorubicin group (5.6%) underwent radical cystectomy for local urothelial progression. One patient (1.8%) in the same group died of distant progression. Our preliminary results suggest that at the dose, periodicity and duration used in the study bacillus Calmette-Guerin is significantly superior to the chemotherapeutic agents doxorubicin and thiotepa for the prophylaxis of recurrence and retardation of progression in superficial transitional cell bladder tumors.