A phase I study of weekly docetaxel, 24-hour infusion of high-dose fluorouracil/leucovorin and cisplatin in patients with advanced gastric cancer
A phase I study of weekly docetaxel, 24-hour infusion of high-dose fluorouracil/leucovorin and cisplatin in patients with advanced gastric cancer
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DOI：
10.1159/000065471
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发表时间：
2002-01-01
期刊：
影响因子：
3.5
通讯作者：
Chang, JY
中科院分区：
文献类型：
--
作者：
Chen, LT;Liu, TW;Chang, JY
目的：确定多西紫杉醇、5-FU/亚叶酸蛋白和顺铂（DFLP）方案中，多西紫杉醇和5-氟尿嘧啶（5-FU）的最大耐受剂量（MTD）和剂量限制毒性（DLT），每3周给药2周。患者和方法：共有31例未接受化疗的晚期胃腺癌患者参加了这项研究。在整个研究过程中，顺铂和亚叶酸素的剂量分别固定在30和300 mg/m(2)。5-FU剂量固定为1600 mg/m(2)，多西他赛每周1小时输注剂量分别为30、40和50 mg/m(2)，以确定MTD。顺铂、5-FU和亚叶酸素在多西紫杉醇后24小时连续输注。将多西他赛剂量设定在MTD后，评估每周5-FU剂量为1,600、2,000和2,400 mg/m(2)。结果：共进行了95个化疗周期，每位患者中位数为3个周期。多西紫杉醇的MTD为40 mg/m2。当多西他赛剂量为50mg /m2 /周时，发生4级发热性中性粒细胞减少症和3级低镁血症的剂量限制事件。多西紫杉醇固定剂量为40 mg/m2时，5-FU的DLT为2,400 mg/m2 /周。这导致4级中性粒细胞减少，因此5-FU的MTD被定义为2,000 mg/m2。14例（45%）出现3/4级中性粒细胞减少，2例出现发热性中性粒细胞减少。在多西他赛后立即输注顺铂和5-FU/亚叶酸蛋白24小时治疗的首批22例患者中，分别有9例（41%）和4例（18%）患者出现2级和3级低镁血症和低钾血症。在5-FU/亚叶酸钙输注后顺铂给药计划改为3小时输注后，9名随后治疗的患者未观察到此类并发症。2级腹泻11例（35%）。9例（30%）出现2/3级乏力，经纠正电解质紊乱后缓解。26例患者可进行反应分析。完全应答2例（7.8%），部分应答14例（53.8%），总应答率为61.5%（95%可信区间为41.5 ~ 81.6%）。在所有剂量水平下均观察到反应。结论：连续两周每3周输注DFLP似乎是一种有效的方案，对晚期胃癌具有可耐受的毒性。对于进一步的11期研究，该组合的推荐剂量为每周40mg /m(2)多西紫杉醇和2000mg /m(2) 5-FU。版权所有(C) 2002 S. Karger AG，巴塞尔。
Objectives: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of both docetaxel and 5-fluorouracil (5-FU) when administered weekly in a regimen of docetaxel, 5-FU/leucovorin and cisplatin (DFLP) for 2 consecutive weeks every 3 weeks. Patients and Methods: A total of 31 patients with chemo-naive, advanced adenocarcinoma of the stomach were enrolled in the study. Cisplatin and leucovorin dosages were fixed throughout the study at 30 and 300 mg/m(2), respectively. 5-FU dosage was fixed at 1,600 mg/m(2) while docetaxel was evaluated at weekly 1-hour infusion dosages of 30, 40 and 50 mg/m(2) to determine the MTD. Cisplatin, 5-FU and leucovorin were administered together as a 24-hour continuous infusion following docetaxel. Weekly 5-FU dosages of 1,600, 2,000 and 2,400 mg/m(2) were then evaluated after setting the docetaxel dosage at the MTD. Results:A total of 95 chemotherapy cycles were administered, with a median of three cycles per patient. The MTD of docetaxel was defined at 40 mg/m2. At a docetaxel dosage of 50 mg/m2 per week, the dose-limiting events of grade 4 febrile neutropenia and grade 3 hypomagnesemia occurred. With fixation of docetaxel to 40 mg/m2, the DLT for 5-FU was found at 2,400 mg/m2 per week. This incurred grade 4 neutropenia such that the MTD of 5-FU was defined at 2,000 mg/m2. Grade 3/4 neutropenia occurred in 14 patients (45%), with 2 patients developing febrile neutropenia. Grade 2 and 3 hypomagnesemia and hypokalemia occurred in 9 (41%) and 4 (18%) patients, respectively, of the first 22 patients treated with a 24-hour infusion of cisplatin and 5-FU/leucovorin immediately following docetaxel. Following a change in the cisplatin administration schedule to a 3-hour infusion after 5-FU/leucovorin infusion, no such complications were observed in 9 subsequently treated patients. Grade 2 diarrhea was recorded in 11 patients (35%). Grade 2/3 asthenia occurred in 9 patients (30%), which resolved after correction of electrolyte disorders. Twenty-six patients were assessable for response analysis. There were 2 (7.8%) complete and 14 (53.8%) partial responses, with the overall response rate being 61.5% (95% confidence interval, 41.5-81.6%). Responses were observed at all dose levels. Conclusion: Two consecutive weeks of DFLP infusions every 3 weeks appear to be an active regimen with a tolerable toxicity profile in advanced gastric cancer. For further phase 11 studies, the recommended dose for this combination is 40 mg/m(2) of docetaxel and 2,000 mg/m(2) of 5-FU per week. Copyright (C) 2002 S. Karger AG, Basel.