Lin Chia-Chi, Hsu Chih-Hung, Hour Tzyh-Chyuan, Cheng Ann-Lii, Huang Chao-Yuan, Huang Kuo-How, Chen Jun, Pu Yeong-Shiau
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Urol Oncol. 2007 May-Jun;25(3):207-13. doi: 10.1016/j.urolonc.2006.06.002.
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.
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%.
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.
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.
