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 combination chemotherapy as first-line treatment id advanced urothelial cancer. Pa tients and methods. Thirty-four patients with histologically confirmed advanced urothelial cancer, with measurable disease and without previ ous chemotherapy entered the study; all 34 are evaluable. The 28 males and 6 females had a median age of 65 (19-75) and a median ECOG perfor mance status of 1 (0-2). Twenty-eight patients had bladder cancer, fou r had renal pelvic cancer and two ureteral cancer. Thirty patients had transitional cell carcinoma and four mixed, mostly of grade 3. Sites of disease included lymph nodes (18), bladder (9), liver (9), pelvic m ass (9), lung (7), etc. The treatment plan was as follows: 5-fluoroura cil 500 mg/m(2) continuous infusion D1-D5 and D22-D26; interferon-alph a-2b 5 million I.U./m(2) D1-D5 followed by 3x/week and then D22-D26; c isplatin 25 mg/m(2) D1, D8, D15, D22. Cycles were repeated every 36 da ys. Results. The median number of cycles administered was 3 (1-6). The relative dose intensities for 5-fluorouracil, interferon and cisplati n were 76%, 71% and 75%, respectively. Twenty-two of 34 patients (65%, 95% confidence interval [95% CI], 46% to 80%) bad objective responses , including six complete clinical responses (CR) (18%, 95% CI, 7% to 3 5%) and 16 partial responses (PR) (47%, 95% CI, 30% to 65%). Three pat ients had stable disease and seven progressed. Two patients discontinu ed treatment after the first cycle because of toxicity. The median sur vival is 15.30 months (1.40-37.60), the median time to progression 11. 60 months (4.13-37.60); and the median survival of complete responders 20.75+ months (8+ to 38+). The only significant hematologic toxicity was the grade 3-4 neutropenia in 44%. Non-hematologic toxic effects we re unremarkable. Conclusion. The FAP combination as first-line chemoth erapy is highly active in the treatment of advanced urothelial cancer, and has limited toxicity. Further phase III studies are in progress t o compare FAP and M-VAC.