BCG versus epirubicin in the prophylaxis of multiple superficial bladder tumours: Results of a prospective randomized study using modified treatment schemes

Abstract

A prospective randomized trial on 94 eligible patients evaluated and compared the efficacy of adjuvant intravesical epirubicin and bacillus Calmette-Guérin (BCG) after complete resection of multifocal superficial bladder cancer. BCG treatment schedule consisted of an induction 6-week course of instillations (150 mg Pasteur BCG per instillation) and single maintenance doses to patients who remained free of recurrences at follow-up examinations for a total treatment period of 2 years. These initial responders received additionally a separate 4-week course of therapy 6 months after the start of treatment. Chemoprophylaxis included an early (on the second postoperative day) instillation followed by 4 weekly treatments with epirubicin (50 mg per instillation) and then by 10 monthly treatments for the initial responders during the first year of follow-up and at every follow-up examination for a total treatment period of 2 years. The overall treatment results did not differ significantly between the 2 arms (54% of patients of the epirubicin group remained free of recurrences compared to 65% of those treated with BCG) for an identical mean follow-up of 35.1 months. However, a significant benefit in favour of BCG when compared with epirubicin was shown in patients who had stage T1 and grade 3 tumours and in terms of relative risk of recurrences, disease-free interval and recurrence rate per 100 patient-months. Both drugs were proved to be safe with manageable toxicity.

Intravesical Therapy of Superficial Bladder Cancer

“…The same trends were found in all patientsubgroups examined. In controlled prospective trials of epirubicin chemoprophylaxis after complete TUR of superficial bladder cancer, intravesical instillation of 50 mg given weekly for 6 or 8 consecutive weeks plus single maintenance dose at every follow-up examination to patients remaining free of recurrences have yielded remarkably lower mean interval to tumor recurrence and recurrence rate per 100 patient-months than those seen in patients who did not receive epirubicin, especially among subjects with multiple and/or recurrent neoplasms, for a mean follow-up of up to 3 years [31][32][33][34][35]. However, although intravesical epirubicin…”

“…As far as chemoprophylaxis is concerned , a EORTC-GU Group study, that was conducted to compare the efficacy of TUR alone with that of TUR followed by intravesical doxorubicin or ethoglucid instillations, showed that the time to first tumor recurrence was significantly longer with the use of both drugs [25]: recurrence rate per patient year chemoprophylaxis has reduced short-and intermediate-term tumor recurrence rates, it has not altered disease progression. Like most of the different chemotherapeutic agents used, epirubicin is associated with local irritative symptoms, although less than those with adriamycin [27,28,[30][31][32][33][34][35]. Immediate instillation of a rather high concentration of epirubicin (80 mg) after TUR has caused an only 7% incidence of chemical cystitis [30].…”

The Influence of Intravesical Therapy on Progression of Superficial Transitional Cell Carcinoma of the Bladder

“…Mitomycin C doses ranged from 20 to 40 mg, whereas variation was also seen in BCG dose and schedule. For instance, Melekos et al 23 used only 50 mg of BCG versus 150 mg used by Martinez et al 21 and Melekos et al 22 Time course of treatment differed among investigators as well. As a result of the small number of studies included, no further analysis of treatment schedule was possible.…”

“…19,20,25,26 Other drugs included doxorubicin, thiotepa, and epirubicin with the latter drug used in 3 study arms. 22,23,27 Treatment schedules are also outlined in Table 1. Mitomycin C doses ranged from 20 to 40 mg, whereas variation was also seen in BCG dose and schedule.…”

“…As seen in Table 2, mean/median follow-up times ranged from 30 to 86 months with half of the available reports having follow-up times of 3 years of less. 19,21,22,25 Initially, data from all 8 randomized trials were pooled using tumor progression as the outcome of interest (2427 patients total). The summary odds ratio for this analysis was 1.24 with a 95% confidence interval of 0.95-1.61, a nonstatistically significant result (see Fig.…”