Intravesical Bacillus Calmette-Guérin versus Epirubicin in the Prophylaxis of Recurrent and/or Multiple Superficial Bladder Tumours

Abstract

A prospective, randomized trial was conducted to evaluate and compare the effects of modified adjuvant intravesical bacillus Calmette-Guerin (BCG) and epirubicin regimens in patients with superficial bladder cancer. One hundred thirty-two individuals with recurrent and/or multiple neoplasms, i.e. at high risk for tumour recurrence and progression, were enrolled. After complete transurethral resection of their tumours, the patients received a 6-week course of BCG instillations or an early 4-week course of epirubicin instillations as their initial therapy. Those with stage Ta and grade 1 neoplasms who remained free of recurrences received maintenance therapy consisting of single quarterly instillations. However, for those with stage T1 cancer of any grade or stage Ta of grade 2 or 3 neoplasms who also remained free of recurrences, the treatment schedules were modified: they received, instead of single maintenance doses, 3 weekly instillations of epirubicin at months 3 and 6 of follow-up, or a 3-week course of BCG at month 6 of follow-up. The recurrence-free rates did not differ significantly between the two study groups (44% for epirubicin versus 55% for BCG), for an identical median follow-up of 43 months. However, in terms of relative risk of recurrences, disease-free intervals and recurrence rate per 100 patient-months, a significant benefit in favour of BCG when compared with epirubicin was demonstrated in patients who had stage T1 or grade 3 neoplasms.

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 rates of responses, however, decrease with time to about 50% and Intravesical BCG has a mechanism of action unlike that of chemotherapeutic agents and the symptoms of side-effects associated with are therefore, not unexpectedly different. Irritative bladder symptoms, such as dysuria and urinary frequency, are common and range from 40% to 90% [13,23,[33][34][35]49,56,61]. These symptoms are typically produced after the third BCG instillation and are mild and brief since they are a consequence of the immune stimulation (and inflammatory reaction).…”

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

“…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.…”

“…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.…”