Irinotecan combined with bolus fluorouracil, continuous infusion fluorouracil, and high-dose leucovorin every two weeks (LV5FU2 regimen):: A clinical dose-finding and pharmacokinetic study in patients with pretreated metastatic colorectal cancer
Irinotecan combined with bolus fluorouracil, continuous infusion fluorouracil, and high-dose leucovorin every two weeks (LV5FU2 regimen):: A clinical dose-finding and pharmacokinetic study in patients with pretreated metastatic colorectal cancer
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DOI：
10.1200/jco.1999.17.9.2901
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发表时间：
1999-09-01
影响因子：
45.3
通讯作者：
Rougier, P
中科院分区：
文献类型：
--
作者：
Ducreux, M;Ychou, M;Rougier, P
目的：确定伊立替康 (CPT-11) 联合氟尿嘧啶 (5-FU) 和亚叶酸 (LV) 的最大耐受剂量 (MTD) 和推荐剂量，采用每两周一次的 LV5FU2 方案和增加 CPT-11 的剂量，并评估该组合在经治疗的结直肠癌 (CRC) 患者中的疗效。 患者和方法：所有患者均患有转移性 CRC，世界卫生组织的体能状态为0 或 1，每两周以一定剂量水平（100、120、150、180、200、220 和 260 mg/m(2)）进行 90 分钟输注 CPT-11，每两周 CPT-11 输注结束后 1 小时开始 LV5FU2，并在第 2 天进行，结果：55 名患者参加了本次试验；进行了 549 个周期，MTD 未达到 260 mg/m(2)，因此添加了 300 mg/m(2) 的剂量水平。在此剂量水平下也未达到方案中定义的 MTD，但所有患者的周期均延迟和/或需要减少剂量，该剂量被视为 MID。考虑到每两周一次的毒性和依从性，推荐的 CPT-11 剂量设定为 180 至 200 mg/m(2)。几乎所有剂量水平均观察到抗肿瘤活性，客观缓解率为22%，中位进展时间为6.3个月，总生存期为15个月。结论：每两周一次的CPT-11/LV5FU2组合是可行且安全的，无重叠毒性。选择180至200 mg/m(2)的CPT-11与LV5FU2组合作为进一步研究的推荐剂量。 (C) 1999 年，美国临床肿瘤学会。
Purpose: To determine the maximum-tolerated dose (MTD) and recommended dose of irinotecan (CPT-11) in combination with fluorouracil (5-FU) and leucovorin (LV), using a biweekly LV5FU2 regimen and increasing doses of CPT-11, and to assess the efficacy of this combination in pretreated patients with colorectal cancer (CRC).Patients and Methods: All patients had metastatic CRC and a World Health Organization performance status of 0 or 1, CPT-11 was administered over a 90-minute infusion every 2 weeks at a range of dose levels(100, 120, 150, 180, 200, 220, and 260 mg/m(2)), LV5FU2 was started 1 hour after the end of the biweekly CPT-11 infusion and was also administered on day 2,Results: Fifty-five patients were entered onto this trial; 549 cycles were administered, The MTD was not reached at 260 mg/m(2), and a dose level of 300 mg/m(2) was added. The MTD as defined in the protocol was not reached at this dose level either, but all patients had cycles delayed and/or required a dose reduction, This dose was deemed to be the MID. To take into account both the toxicity of and compliance with the biweekly schedule, the recommended CPT-11 dose wets established at 180 to 200 mg/m(2). Antitumor activity was observed at almost all dose levels, with an objective response rate of 22%, Median time to progression was 6.3 months and overall survival was 15 months,Conclusion: The biweekly CPT-11/LV5FU2 combination is feasible and safe, without overlapping toxicity CPT-11 at 180 to 200 mg/m(2) in combination with LV5FU2 has been selected as the recommended dose for further studies. (C) 1999 by American Society of Clinical Oncology.