Ifosfamide in the treatment of bladder cancer

Although chemotherapy for advanced bladder cancer has historically been based on cisplatin-based combination regimens, the limitations of these regimens both in terms of efficacy and toxicity are now widely appreciated. In response to these limitations, other single agents have been studied, and a number have demonstrated significant activity, including ifosfamide. Older single-agent phase II trials of ifosfamide in previously untreated patients suggested a response rate as high as 40%, including objective responses in nontransitional histologies. More recently, the Eastern Cooperative Ontology Group has defined the response rate for ifosfamide in patients with one prior chemotherapy regimen to be 20%, with central nervous system toxicity, nephrotoxicity, and myelosuppression as the dose-limiting toxicities. Phase II trials of ifosfamide in combination with vinblastine and gallium nitrate have been completed, while others, including trials with paclitaxel alone or paclitaxel plus cisplatin, are ongoing. The precise role of ifosfamide in the therapy of advanced bladder cancer is in the process of being defined. However, the frequency of occult or clinically evident renal insufficiency in this patient population may limit ifosfamide's role in this disease.