Non-transitional cell carcinomas account for 5% to 10% of urothelial tract tumors and are each characterized by unique demographics, risk factors, and patterns of spread. A unifying feature of these malignancies is their aggressive course and poor outcome with standard chemotherapeutic regimens. Given the rarity of these tumors, no prospective data are available to guide management.

Patients with unresectable/metastatic adenocarcinoma or squamous cell, small cell, sarcomatoid, or poorly differentiated carcinoma of the urothelial tract were eligible for enrollment. Treatment consisted of paclitaxel 200 mg/m2 intravenously on day 1, cisplatin 70 mg/m2 intravenously on day 1, ifosfamide 1500 mg/m2 intravenously on days 1 to 3 plus mesna. Granulocyte colony-stimulating factor was administered with each cycle. The treatment was started again every 3 to 4 weeks for a maximum of six cycles.

A total of 20 patients were enrolled. They had the following histologic types: adenocarcinoma in 11, squamous cell carcinoma in 8, and small cell carcinoma in 1. Patients received a median of four cycles (range one to six). The treatment was generally well tolerated, and the toxicity was predominantly hematologic. Overall, 7 (35%) of 20 patients (95% confidence interval 15% to 59%) achieved a major response (3 partial and 4 complete). The median survival for patients with adenocarcinoma was 24.8 months (95% confidence interval 10.2 to 32.3), and for those with squamous cell carcinoma it was 8.9 months (95% confidence interval 5.4 to not yet reached).

The results of our study have shown that this regimen (ifosfamide, paclitaxel, and cisplatin) is active in patients with advanced non-transitional cell carcinoma of the urothelial tract. To our knowledge, this is the first prospective study of a chemotherapeutic regimen in this patient population.