Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: a phase 2 study.

PURPOSE: This phase 2 trial was designed to assess the efficacy and safety of combination chemotherapy with docetaxel and ifosfamide in previously treated patients with advanced urothelial cancer.
MATERIALS AND METHODS: Enrolled in our study were 22 patients with advanced urothelial cancer who failed to respond or had relapse after previous platinum based chemotherapy. Treatment consisted of 60 mg./m.2 docetaxel given during 1 hour and 2.5 gm./m.2 ifosfamide given for 24 hours every 3 weeks with 500 mg. mesna administered intravenously at the start of the ifosfamide infusion, and 4 and 8 hours later. Patients also received premedication with oral dexamethasone.
RESULTS: The objective response rate in 20 evaluable patients was 25%, including 4 complete responses (20%) associated with lymph node only recurrence. Disease was stable in 5 cases. At followup 16 patients had died 1 to 11 months (median 4) after the initiation of treatment, while 6 remained alive at 4 to 14 months, including 3 who were continuously disease-free. Treatment was well tolerated. Grades 3 and 4 leukopenia developed in 17% and 4% of the cycles, respectively. Neutropenic sepsis and grade 4 thrombocytopenia developed in 1 case each. Nausea and vomiting were mild to moderate. Other nonhematological toxicities included a hypersensitivity reaction in 1 patient and paresthesias in 2.
CONCLUSIONS: The combination of docetaxel and ifosfamide is active in previously treated patients with urothelial cancer, although it appears to be a reasonable treatment option only in those with lymph node dominant recurrence. The mild toxicity underlines the usefulness of the regimen in this setting. Further investigation of the combination in previously untreated patients seems warranted.