title: Weekly paclitaxel and high-dose 5-fluorouracil plus leucovorin in hormone-refractory prostate cancer: in vitro combined effects and a phase II trial.
abstract: OBJECTIVE
  Paclitaxel and 5-fluorouracil have been used to treat hormone-refractory prostate cancer with some success. In vitro data suggest that the combined cytotoxicity may be sequence dependent. Thus, we explored the combined effects of the 2 agents, both in vitro and in vivo.
  
  
  METHODS
  The combined cytotoxicity of paclitaxel and 5-fluorouracil, and the possible schedule dependence were studied in vitro using PC-3 and DU145 cells and the microculture tetrazolium assay. There were 23 patients with hormone-refractory prostate cancer treated with the regimen T-HDFL: paclitaxel 90 mg/m2 intravenously 1 hour on days 1 and 8; 5-fluorouracil 2000 mg/m2; and leucovorin 300 mg/m2 intravenous 24-hour infusion on days 2 and 9, which repeated every 21 days. The allowed percentage of bone marrow irradiation was 50%.
  
  
  RESULTS
  Significant synergistic cytotoxicity was seen only when paclitaxel was given 24 hours before 5-fluorouracil. With the T-HDFL regimen, 11 (52%) of the 21 evaluable patients had > or = 50% reduction of prostate-specific antigen, lasting for 6 weeks. Of the 7 patients with measurable disease, 2 had a partial response. Median overall survival was 14.1 months. Grade III/IV leukopenia occurred in 2 patients. There was no treatment-related death. Toxicities were well tolerated.
  
  
  CONCLUSIONS
  The combined cytotoxicity of paclitaxel and 5-fluorouracil is schedule dependent. It is feasible to administer weekly paclitaxel and high-dose 5-fluorouracil infusions in patients with hormone-refractory prostate cancer. Our findings may serve as an important rationale for future trial design.
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: Tzyh-Chyuan
authors.initials: TC
authors.lastname: Hour
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.forename: Kuo-How
authors.initials: KH
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Yeong-Shiau
authors.initials: YS
authors.lastname: Pu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000188:drug therapy*
chemical_list: D017239:Paclitaxel; D002955:Leucovorin; D005472:Fluorouracil