Palliative chemotherapy in advanced bladder cancer

Transitional cell carcinoma of the urothelium is a chemosensitive tumor, and combination chemotherapy can provide not only palliation but a modest survival advantage in patients with advanced disease. While the four-drug regimen methotrexate/vinblastine/doxorubicin/cisplatin remains the standard combination therapy, its toxicity can be formidable. The overall response rate in phase III trials with this combination is in the 35% to 45% range, with a median survival duration in treated patients of only 12 months. Although attempts to decrease the toxicity of the regimen with the addition of hematopoietic growth factors have been successful, attempts to increase its efficacy by dose escalation have not. This has prompted a search for new active agents that can be incorporated into alternative combination regimens. Recently, activity has been noted for several drugs (including gallium nitrate, ifosfamide, and gemcitabine). In untreated patients, paclitaxel has demonstrated significant activity and is certainly among the most active single agents in the treatment of advanced bladder cancer. Studies incorporating these new agents into novel combination regimens are ongoing, with the goal of providing a regimen that has superior efficacy in advanced disease and, ultimately, in earlier stages of disease with curative intent.