5-Fluorouracil, interferon-{alpha}-2b and cisplatin (FAP) for advanced urothelial cancer. A phase II study

Purpose: To evaluate the efficacy and toxicity of the FAP combinationchemotherapy as first-line treatment in advanced urothelial cancer.Patients and methods: Thirty-four patients with histologicallyconfirmed advanced urothelial cancer, with measurable disease and withoutprevious chemotherapy entered the study; all 34 are evaluable. The 28 malesand 6 females had a median age of 65 (19–75) and a median ECOGperformance status of 1 (0–2). Twenty-eight patients had bladder cancer,four had renal pelvic cancer and two ureteral cancer. Thirty patients hadtransitional cell carcinoma and four mixed, mostly of grade 3. Sites ofdisease included lymph nodes (18), bladder (9), liver (9), pelvic mass (9),lung (7), etc. The treatment plan was as follows: 5-fluorouracil 500mg/m² continuous infusion D1–D5 and D22–D26;interferon--2b 5 million I.U./m² D1–D5 followed by3×/week and then D22–D26; cisplatin 25 mg/m² D1,D8, D15, D22. Cycles were repeated every 36 days.Results: The median number of cycles administered was 3 (1–6).The relative dose intensities for 5-fluorouracil, interferon and cisplatinwere 76%, 71% and 75%, respectively. Twenty-two of 34patients (65%, 95% confidence interval [95% CI],46% to 80%) had objective responses, including six completeclinical responses (CR) (18%, 95% CI, 7% to 35%)and 16 partial responses (PR) (47%, 95% CI, 30% to65%). Three patients had stable disease and seven progressed. Twopatients discontinued treatment after the first cycle because of toxicity. Themedian survival is 15.30 months (1.40–37.60), the median time toprogression 11.60 months (4.13–37.60), and the median survival ofcomplete responders 20.75+ months (8+ to 38+). The only significanthematologic toxicity was the grade 3–4 neutropenia in 44%.Non-hematologic toxic effects were unremarkable.Conclusion: The FAP combination as first-line chemotherapy is highlyactive in the treatment of advanced urothelial cancer, and has limitedtoxicity. Further phase III studies are in progress to compare FAP and M-VAC.