The role of ifosfamide in the treatment of testicular and urothelial malignancies.
The activity of ifosfamide in genitourinary malignancies has been documented in testicular cancer and bladder cancer. The use of ifosfamide in germ cell tumors spans 20 years and has involved three distinct clinical settings: as a component of salvage therapy in cisplatin-resistant or recurrent disease, as part of initial therapy for patients with poor-risk disease, and as part of an ablative regimen for patients undergoing high-dose therapy with stem cell support. The use of ifosfamide in salvage therapy is well established, with approximately 40% to 50% of patients treated with a second-line ifosfamide-based regimen expected to achieve a complete response; however, only 25% of these patients will be long-term disease-free survivors. The drug's incorporation into standard-dose first-line regimens in patients with poor-risk disease has failed to improve the efficacy of therapy over standard, less toxic regimens. The value of ifosfamide as a component of high-dose salvage therapy with stem cell support in patients with refractory disease or of its increasing use as first-line therapy in patients with poor-risk features remains to be demonstrated. In urothelial carcinoma, data on the activity of ifosfamide are more sparse. Older trials in previously untreated patients in Japan and Egypt suggest an overall response rate of 30% to 40%, while a recent Eastern Cooperative Oncology Group trial in patients with prior chemotherapy reported a response rate of 20%. Ifosfamide has therefore been identified as one of six new active agents in urothelial cancer, and trials of combination regimens including ifosfamide are under way. The vinblastine/ifosfamide/gallium nitrate (VIG) combination was tested in a pilot study at Indiana University with a 67% overall response rate and in a confirmatory Eastern Cooperative Oncology Group phase II trial with a 56% response rate. Trials of ifosfamide plus paclitaxel with or without cisplatin are ongoing, but the role of ifosfamide in the routine therapy of urothelial malignancies remains to be determined.
Roth
B J
BJ
Division of Hematology/Oncology, Indiana University Medical Center, Indianapolis, USA.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy; D002986:Clinical Trials as Topic; D018237:Germinoma / Q000188:drug therapy; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage*; D008297:Male; D016879:Salvage Therapy; D013736:Testicular Neoplasms / Q000188:drug therapy*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D007069:Ifosfamide