Delayed High-Dose Intravesical Epirubicin Therapy of Superficial Bladder Cancer

Abstract

Introduction: Intravesical epirubicin is a widely used agent for the treatment of superficial bladder cancer. A direct relationship between dose and activity has been reported: unfortunately the dose increase also increased the frequency and the intensity of treatment-related side effects. Materials and Methods: A phase 2 trial was designed to evaluate the toxicity and the activity of a delayed (biweekly) high-dose (80 mg) epirubicin therapy of superficial bladder cancer. Thirty patients with intermediate risk superficial bladder cancer (stage mTa, G2) have been treated with transurethral resection and epirubicin intravesical therapy: the patients were given 80 mg epirubicin in 50 ml sterile saline every 2 weeks for 6 times (delayed regimen). The follow-up ranged from 3 to 26 months. Eleven of 30 (37%) patients experienced a local adverse reaction to intravesical epirubicin requiring specific medication (grade ≧2 according to NCI-CTC v.2.0, 1999). No systemic toxicity related to the treatment was observed. Results: Out of the 29 evaluable patients, 22 (76%) were free of disease after the induction course, 6 (21%) had superficial bladder cancer recurrences and 1 (3%) experienced tumor progression. Conclusion: A delayed (biweekly instillation) high-dose (80 mg) intravesical epirubicin regimen was acceptable in terms of side effects and showed a worthwhile therapeutical impact in patients with intermediate risk superficial bladder cancer.

Drug Resistance and Cellular Adaptation to Tumor Acidic pH Microenvironment

“…Epirubicin is used clinically to treat breast cancer and has been investigated as a treatment for superficial bladder cancer via intravesical delivery 63, 64 . In-vitro studies show that epirubicin exhibits increased efficacy against human bladder cancer cells 65, 66 and chineese hamster ovary cells cultured under alkaline conditions 67 .…”