Intravesical epirubicin versus doxorubicin for superficial bladder tumors (stages pTa and pT1): A randomized prospective study

Purpose: We performed a prospective, randomized, controlled study to compare intravesical epirubicin and doxorubicin as adjuvant therapy after endoscopic resection of superficial bladder tumor. Materials and Methods: We randomly allocated 253 eligible patients to 4 study arms. Seven to 14 days after transurethral bladder tumor resection instillation of the intravesical agent was instituted, including 50 and 80 mg. epirubicin in study arms 1 and 2, respectively, and 50 mg. doxorubicin in arm 3. Control arm 4 included patients who underwent transurethral bladder tumor resection alone. Instillation was repeated weekly for 8 weeks and monthly thereafter to complete 1 year of treatment. All patients were followed every 3 months by cystourethroscopy, urine cytology and deoxyribonucleic acid flow cytometry for 12 to 48 months (mean 30.1). Results: Rates of recurrence were significantly lower in the chemotherapy groups than in controls (p < 0.001) and in the epirubicin groups than in the doxorubicin group (p = 0.02). In arms 1 to 4 recurrence rates were 25, 17.6, 36.7 and 65.6%, respectively. Recurrence rates per 100 patient months were 0.83, 0.60, 1.18 and 2.73, respectively, which were significant statistically, and lower after chemotherapy in general and epirubicin in particular (p < 0.05). Mean interval to first recurrence was 16, 15.4, 18.9 and 6.3 months, respectively, with a significant difference between the chemotherapy and control groups (p < 0.05). Progression to muscle invasive disease occurred in 7 (10.9%), 3 (4.4%), 6 (10%) and 5 patients (8.2%), respectively, in arms 1 to 4 (p > 0.05). We studied the relationships among different risk factors, and patterns of recurrence and progression. For pT1 tumors recurrence rates in arms 1 to 4 were 26.3, 17.8, 39.3 and 70.9%, respectively, which were significantly lower in the chemotherapy group than in controls (p < 0.001) and in the epirubicin groups than in the doxorubicin group (p = 0.01). Toxic and untoward side effects developed in 10 (15.6%), 16 (23.5%) and 25 (41.7%) patients in chemotherapy arms 1 to 3, respectively, with a marginal insignificant difference between low and high dose epirubicin (p = 0.3), and significantly lower toxicity rates in arms 1 and 2 than in 3 (p = 0.002). A contracted bladder developed in 2.1% of all patients who received chemotherapy. Conclusions: This study demonstrates that epirubicin has better efficacy and lower toxicity than doxorubicin when used as an intravesical agent.