Phase I/II study of S-I combined with irinotecan for metastatic advanced gastric cancer
Phase I/II study of S-I combined with irinotecan for metastatic advanced gastric cancer
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DOI：
10.1038/sj.bjc.6603072
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发表时间：
2006-04-24
影响因子：
8.8
通讯作者：
Sugihara, K
中科院分区：
文献类型：
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作者：
Inokuchi, M;Yamashita, T;Sugihara, K
进行了伊立替康（CPT-11）联合S-1（一种口服二氢嘧啶脱氢酶抑制剂氟嘧啶）的剂量递增研究，以确定晚期胃癌（AGC）的最大耐受剂量（MTD）、推荐剂量（RD）、剂量限制性毒性（DLT）和客观缓解率（RR）。S-1在28天周期的第1 - 14天以80 mg m（-2）day（-1）口服给药，CPT-11在第1和8天以70 mg m（-2）day（-1）的初始剂量静脉给药，逐步增加至100 mg m（-2）。除非观察到疾病进展，否则每4周重复治疗。在I期部分，CPT-11的MTD被假定为100 mg m（-2），因为66.6%的患者（2/3）发生DLT。CPT-11初始RD（90 mg m（-2））的所有3例患者在第二个疗程时均发生4级血液学或3级非血液学毒性，随后从第三个疗程开始减少CPT-11的剂量。考虑到安全性和继续治疗的能力，最终RD确定为80 mg m（-2）。在II期部分，评价了42例患者，包括最终RD I期部分的7例患者。中位疗程为5（范围：1-13）。重度（3-4级）血液学和非血液学毒性的发生率分别为19%和10%，但均可控。RR为62%（26/42，95%置信区间：47.2-76.6%），中位生存期为444天。我们的I/II期试验显示S-1联合CPT-11治疗AGC有效，耐受性良好，毒性可接受。
A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was administered orally at 80 mg m(-2) day(-1) from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m(-2) day(-1), stepping up to 100 mg m(-2). The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m(-2), because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m(-2)) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m(-2). In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1-13). The incidences of severe (grade 3-4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2-76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity.