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 tre ated 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 plat inum based chemotherapy. Treatment consisted of 60 mg./m.(2) docetaxel give n during 1 hour and 2.5 gm./m.(2) ifosfamide given for 24 hours every 3 wee ks with 500 mg. mesna administered intravenously at the start of the ifosfa mide infusion, and 4 and 8 hours later. Patients also received premedicatio n with oral dexamethasone. Results: The objective response rate in 20 evaluable patients was 25%, incl uding 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 m onths (median 4) after the initiation of treatment, while 6 remained alive at 4 to 14 months, including 3 who were continuously disease-free. Treatmen t was well tolerated. Grades 3 and 4 leukopenia developed in 17% and 4% of the cycles, respectively. Neutropenic sepsis and grade 4 thrombocytopenia d eveloped in 1 case each. Nausea and vomiting were mild to moderate. Other n onhematological toxicities included a hypersensitivity reaction in 1 patien t and paresthesias in 2. Conclusions: The combination of docetaxel and ifosfamide is active in previ ously treated patients with urothelial cancer, although it appears to be a reasonable treatment option only in those with lymph node dominant recurren ce. The mild toxicity underlines the usefulness of the regimen in this sett ing. Further investigation of the combination in previously untreated patie nts seems warranted.