Phase I study of adjuvant gemcitabine or S-1 in patients with biliary tract cancers undergoing major hepatectomy: KHBO1003 study
Phase I study of adjuvant gemcitabine or S-1 in patients with biliary tract cancers undergoing major hepatectomy: KHBO1003 study
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DOI：
10.1007/s00280-014-2543-4
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发表时间：
2014-10-01
影响因子：
3
通讯作者：
Ioka, Tatsuya
中科院分区：
文献类型：
--
作者：
Kobayashi, Shogo;Nagano, Hiroaki;Ioka, Tatsuya
胆道癌（BTC）肝切除术后不进行标准化辅助治疗，因为频繁的不良事件，这可能是由肝功能不足引起的。因此，本多中心研究的目的是（KHBO 1003）的目的是确定肝大部切除术后辅助化疗的安全性方案。（半肝切除术或三部分切除术）治疗BTC，进行以下辅助化疗6个月：吉西他滨800- 1，000 mg/m2，第1、8和15天，然后每3-4周一次，或S-1 40-80 mg/m2/天，第1-28天，每3-6周一次。主要剂量限制性毒性（DLT）定义为4级血液毒性、3/4级发热性中性粒细胞减少症、3/4级非血液毒性、第8天和第15天停用吉西他滨或在第14天或之后停止疗程。剂量递增和递减决定基于持续再评估方法。2011年2月至2012年7月，33例患者（14例肝内胆管，1例胆囊，18例肝外胆管）入组本研究（n = 18吉西他滨，n = 15 S-1）。在10%的DLT时，推荐剂量为1，000 mg/m2吉西他滨每两周一次，80 mg/m2/天S-1第1-28天和每6周一次。主要DLT和药物不良反应为中性粒细胞减少。没有发现3级或4级非血液学不良事件，我们确定了肝切除术后吉西他滨和S-1辅助化疗的RD，DLT不超过10%。
Standardized adjuvant therapy is not performed after major hepatectomy for biliary tract cancer (BTC) because of frequent adverse events, which may be caused by insufficient liver function. Therefore, the aim of this multicenter study (KHBO1003) was to determine the safety protocol for adjuvant chemotherapy after major hepatectomy.Within 12 weeks of R0 or R1 major hepatectomy (hemihepatectomy or trisectionectomy) for BTC, the following adjuvant chemotherapy was performed for 6 months: 800-1,000 mg/m(2) gemcitabine on days 1, 8, and 15 and then every 3-4 weeks or 40-80 mg/m(2)/day S-1 on days 1-28 and every 3-6 weeks. Major dose-limited toxicity (DLT) was defined as grade 4 hematotoxicity, grade 3/4 febrile neutropenia, grade 3/4 non-hematotoxicity, skipped gemcitabine on days 8 and 15, or halting the course at or after 14 days. Dose-escalation and de-escalation decisions were based on the continual reassessment method. Every three patients were alternately assigned to each arm.Thirty-three patients (14 intrahepatic bile duct, 1 gall bladder, 18 extrahepatic bile duct) were enrolled in this study from February 2011 to July 2012 (n = 18 gemcitabine, n = 15 S-1). At 10 % of DLT, the recommended dose was 1,000 mg/m(2) gemcitabine biweekly and 80 mg/m(2)/day S-1 on days 1-28 and every 6 weeks. Major DLT and adverse drug reactions were neutropenia. No grade 3 or 4 non-hematological adverse events were noted.We determined RDs for gemcitabine and S-1 adjuvant chemotherapy after major hepatectomy with a DLT that does not exceed 10 %.