Phase II trial of ifosfamide, fluorouracil, and folinic acid (FIFO regimen) in relapsed and refractory urothelial cancer.

There is no known effective salvage chemotherapy for patients with refractory or relapsed urothelial tumors after methotrexate/cisplatin-based regimen. We report the results of a phase II trial with the FIFO regimen that includes from day 1 to 5: fluorouracil 350 mg/m2, folinic acid 20 mg/m2, and ifosfamide 1000 mg/m2, Q4W. Fifteen patients with metastatic measurable urothelial cancer were enrolled in this trial. Previous therapy included M-VAC regimen in 11 patients, CMV regimen in 3 patients, and both regimens in 1 patient. Thirty-one courses were delivered. Toxicity was moderate, including encephalopathy grade 2 in 2 patients and hematological toxicity grade 3 in 2 others. However, an early death occurred on day 1 in a patient who progressed rapidly and died from hepatic insufficiency after initial encephalopathy. No objective response was seen. Twelve patients progressed during FIFO therapy and 3 patients experienced a stable disease. Despite almost encouraging results of fluorouracil and ifosfamide in the literature, their combination according to our schedule is not active in urothelial cancer.