Intravesical Instillations of 4-EPI-Doxorubicin (Epirubicin) in the Prophylactic Treatment of Superficial Bladder Cancer: Results of a Controlled Prospective Study

Abstract

A controlled prospective study in 65 patients was done to evaluate the efficacy of intravesical epirubicin administration as prophylactic treatment in regard to the pattern of tumor recurrences after complete endoscopic resection of superficial transitional cell carcinoma of the bladder. Intravesical instillations of the drug were given weekly for 6 consecutive weeks and to the responders an intermittent maintenance therapy was administered for the first 2 years after each followup examination. Of the patients treated prophylactically with epirubicin 37% had recurrence within a total of 1,136 patient-months compared to 55% of the controls who were followed for a total of 436 months, a difference that was not statistically significant (p greater than 0.05). However, examining the results in another manner, the control patients demonstrated a significantly shorter mean interval to recurrence and higher recurrent tumor rate per 100 patient-months. To clarify further the efficacy of epirubicin therapy, comparisons of the treatment outcome according to several tumor factors were done. These comparisons revealed a significant benefit for those who received epirubicin with respect to history of tumor recurrences and multiplicity at presentation. Drug-induced toxicity was acceptable. Our study suggests that epirubicin is safe and effective against the recurrence of superficial bladder cancer.

Intravesical Combined Chemoimmunotherapy with Epirubicin and Bacillus Calmette-Guérin Is Not Indicated for Superficial Bladder Cancer

“…In one reported study, epirubicin yielded superior therapeutic responses and a lower toxicity profile because it is more lipophilic than doxorubicin [15]. Melekos et al [16] reported that 60-63% of patients treated with epirubicin after TUR remained free of recurrence [17,18]. Recently, 122 patients were studied for their response to a high (2 mg/ml) or standard (1 mg/ml) dose of epirubicin for the treatment of superficial bladder cancer [19].…”

Analysis of prognostic factors related to primary superficial bladder cancer tumor recurrence in prophylactic intravesical epirubicin therapy

“…These results are similar to those reported for other intravesical prophylactic chemotherapy. 4,5,11 Previous studies of recurrence using the surveillance protocol have demonstrated that the recurrence-free rate is approximately 40-50% at 2-3 years and < 30% at 5 years after operation. 2,17,19 In the present study, we did not have a control group in whom chemotherapeutic agents were not administered.…”

“…10 Administration schedules for intravesical epirubicin vary. [11][12][13] We have used low-dose epirubicin (20 mg/instillation) in order to reduce adverse reactions and have already reported a satisfactory prophylactic effect. 14 In the present study, we limited the subjects to patients with primary tumors and analyzed the prognostic factors related to tumor recurrence.…”

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

“…Evidence, however, from previous controlled trials suggests that intracavitary chemotherapy, including epirubicin. has failed to reduce disease progression [3,6,7,[10][11][12]18]. In contrast, few randomized studies have shown that the achieved benefits of adjuvant BCG treatment can be translated into a prolonged decrease in the rate of disease progression [3.…”

“…Epirubicin (4'-epi-doxorubicin) was synthesized with the aim of finding new anthracycline analogues with an improved spectrum of antitumour activity and lower toxicity. Indeed, the antitumour effica cy of this drug has been proved against a variety of neo plasms when used by the intravenous route, with at least similar effects with its parent Adriamycin but with lower toxicity [4], Epirubicin is also effective in preventing tumour recurrences when given intravesicallv to patients with superficial bladder disease [5][6][7][8].…”