Weekly paclitaxel and high-dose 5-fluorouracil plus leucovorin in hormone-refractory prostate cancer: In vitro combined effects and a Phase II trial
Weekly paclitaxel and high-dose 5-fluorouracil plus leucovorin in hormone-refractory prostate cancer: In vitro combined effects and a Phase II trial
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DOI：
10.1016/j.urolonc.2006.06.002
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发表时间：
2007-05-01
影响因子：
2.7
通讯作者：
Pu, Yeong-Shiau
中科院分区：
文献类型：
--
作者：
Lin, Chia-Chi;Hsu, Chih-Hung;Pu, Yeong-Shiau
目的：紫杉醇和5-氟尿嘧啶已被用于治疗难治性前列腺癌，并取得了一定的成功。体外数据表明，联合细胞毒性可能是序列依赖性的。因此，我们探讨了两种药物的联合作用，无论是在体外和在vivo.Patients和方法：紫杉醇和5-氟尿嘧啶的联合细胞毒性，和可能的时间表依赖性进行了研究，在体外使用PC-3和DU 145细胞和微量培养四氮唑测定。23例难治性前列腺癌患者接受T-HDFL方案治疗：紫杉醇90 mg/m2，第1天和第8天静脉输注1小时; 5-氟尿嘧啶2000 mg/m2;亚叶酸钙300 mg/m2，第2天和第9天静脉输注24小时，每21天重复一次。结果：紫杉醇与5-氟尿嘧啶联合应用24 h后，才能产生明显的协同细胞毒作用。采用T-HDFL方案，21例可评价患者中有11例（52%）前列腺特异性抗原下降>= 50%，持续6周。在7例有可测量疾病的患者中，2例有部分缓解。中位总生存期为14.1个月。2例患者发生III/IV级白细胞减少。无治疗相关死亡。结论：紫杉醇和5-氟尿嘧啶的联合细胞毒作用具有时间依赖性。紫杉醇和大剂量5-氟尿嘧啶每周输注治疗难治性前列腺癌是可行的。我们的研究结果可以作为未来试验设计的重要依据。(C)2007爱思唯尔公司All rights reserved.
Purpose: 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.Patients and Methods: The combined cytotoxicity of paclitaxel and 5-fluorouracil, and the possible schedule dependence were studied in vitro using PC-3 and DU 145 cells and the microculture tetrazolium assay. There were 23 patients with hormone-refractory prostate cancer treated with the regimen T-HDFL: paclitaxel 90 mg/m(2) intravenously I hour on days I and 8; 5-fluorouracil 2000 mg/m2; and leucovorin 300 mg/m(2) 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 >= 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. (C) 2007 Elsevier Inc. All rights reserved.