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.
Department of Oncology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan.
Chia-Chi
CC
Lin
Chih-Hung
CH
Hsu
Chao-Yuan
CY
Huang
Ann-Lii
AL
Cheng
Jun
J
Chen
Nicholas J
NJ
Vogelzang
Yeong-Shiau
YS
Pu
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil