title: Phase II trial of weekly paclitaxel, cisplatin plus infusional high dose 5-fluorouracil and leucovorin for metastatic urothelial carcinoma.
abstract: OBJECTIVE
  Conventional chemotherapy for urothelial carcinoma, such as methotrexate, vinblastine, doxorubicin and cisplatin, is associated with significant toxicity. We have previously reported a low toxicity and yet moderately active regimen containing weekly infusional cisplatin and high dose 5-fluorouracil/leucovorin for advanced urothelial carcinoma. We tested the efficacy and toxicity of adding paclitaxel to that regimen.
  
  
  METHODS
  Between April 2000 and December 2004, 44 patients with a median age of 66 years with metastatic urothelial carcinoma were enrolled. The paclitaxel, cisplatin and high dose 5-fluorouracil/leucovorin regimen consisted of 70 mg/m2 paclitaxel daily as a 1-hour infusion on days 1 and 8, 35 mg/m2 cisplatin daily as a 24-hour infusion on days 2 and 9, 2,000 mg/m2 5-fluorouracil daily and 300 mg/m2 leucovorin daily as a 24-hour infusion on days 2 and 9. The cycles repeated every 21 days. A total of 25 patients (64%) had a creatinine clearance of 35 to 60 ml per minute.
  
  
  RESULTS
  A total of 210 cycles (mean 4.8 per patient) were administered. Of the 40 patients eligible for response evaluation 11 (28%) and 19 (48%) were complete and partial responders with an overall response rate of 75% (95% CI 61 to 89). Median overall and progression-free survival in the whole group was 17.0 (95% CI 13.7 to 20.3) and 8.3 months (95% CI 6.4 to 10.2), respectively. Two-year disease-free survival was 15%. Grade 3 or 4 anemia, leukopenia and thrombocytopenia occurred at 23, 30 and 12 cycles, respectively. Nonhematological toxicity included infection, vomiting and diarrhea, etc. There were 2 treatment related deaths.
  
  
  CONCLUSIONS
  Paclitaxel, cisplatin and high dose 5-fluorouracil/leucovorin is an active regimen against metastatic urothelial carcinoma which has an acceptable toxicity profile.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lin
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.forename: Yeong-Shiau
authors.initials: YS
authors.lastname: Pu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000556:secondary*; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014803:Vitamin B Complex / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D014803:Vitamin B Complex; D017239:Paclitaxel; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil