Weekly cisplatin plus infusional high-dose 5-fluorouracil and leucovorin (P-HDFL) for metastatic urothelial carcinoma: an effective regimen with low toxicity.

BACKGROUND: Conventional systemic chemotherapy for metastatic urothelial carcinoma (UC) such as methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) or cisplatin, methotrexate, and vinblastine (CMV) is associated with significant dose-limiting toxicities and even treatment-related death. The authors developed a regimen that was designed to maintain efficacy, while reducing toxicities.
METHODS: Between January 1998 and July 2003, 35 patients (median age, 71 yrs) with metastatic UC were treated with 4-week cycles of P-HDFL (cisplatin 35 mg/m(2), high-dose 5-fluorouracil [5-FU] 2,600 mg/m(2), and leucovorin 300 mg/m(2), on Days 1 and 8, all given by 24-hr infusion). On Day 15, only HDFL was given again.
RESULTS: Among the 32 patients treated with > or = 2 cycles, 9 (28.1%) and 11 (34.4%) were complete and partial responders, respectively, with an overall response rate of 62.5% (95% confidence interval [CI], 45.9-79.2%). The median overall and progression-free survival was 12.3 months (95% CI, 8.2-16.4 mos) and 10.5 months (95% CI, 8.4-12.6 mos), respectively. Toxicity in a total of 121 courses (mean, 3.5 per patient) was modest, with WHO Grade 3 or 4 leukopenia and thrombocytopenia noted in only 1 and 0 patients, respectively. Grade 3 or 4 nausea, vomiting, mucositis, and diarrhea were noted in 3, 2, 0, and 2 patients, respectively. In general, patients tolerated the regimen very well.
CONCLUSIONS: P-HDFL is a moderately active and considerably low-toxic regimen for metastatic UC. The excellent toxicity profile makes it a viable option for patients with poor general conditions. To reach any conclusion, randomized trials comparing P-HDFL with traditional cisplatin-based regimens are necessary. (c) 2006 American Cancer Society.