A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma
A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma
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DOI：
10.1007/s00280-017-3274-0
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发表时间：
2017-04-01
影响因子：
3
通讯作者：
Sueda, Taijiro
中科院分区：
文献类型：
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作者：
Kondo, Naru;Murakami, Yoshiaki;Sueda, Taijiro
目的：探讨吉西他滨、NAB-紫杉醇和S-1(GAS)两周联合新辅助化疗治疗局部晚期胰腺癌的推荐剂量。吉西他滨(2 mg/m(2)，第1天)、NAB-紫杉醇(2 mg/m(2)，第1天)和S-1(mg/d，第1~7天)的计划剂量分别为800/100/60-100和1000/125/60-100。治疗周期每2周重复一次，6个周期后评估可切除性和治疗反应。本研究登记在UMIN临床试验注册中心(UMIN000016630)。我们纳入了16名LAPC患者。在剂量水平1，8名患者中有1名患者出现剂量限制性毒性(DLT)。接下来的8名患者中有一人也经历了剂量水平2的DLT。根据这些结果，水平2被认为是该方案的推荐剂量。在16例患者中，有13例可进行有治愈意图的胰腺切除术。两周一次的气体化疗推荐剂量为：NAB-紫杉醇125 mg/m(2)，吉西他滨1000 mg/m(2)，S-1：1.25m(2)，60 mg；1.25-1.5m(2)，80 mg；1.5m(2)，100 mg，d1-7，每日2次。在本研究中，GAS化疗显示了良好的初步疗效和轻微的毒性，有必要进行进一步的2期试验来研究GAS方案治疗LAPC的疗效。
To determine a recommended dose for a biweekly combination neoadjuvant chemotherapy including gemcitabine, nab-paclitaxel, and S-1 (GAS) for patients with locally advanced pancreatic ductal adenocarcinoma (LAPC).Patients with borderline resectable or unresectable LAPC without distant metastasis were eligible for this study. The planned dosages of gemcitabine (mg/m(2), day 1), nab-paclitaxel (mg/m(2), day 1), and S-1 (mg/day, days 1-7) were 800/100/60-100 at level 1, and 1000/125/60-100 at level 2. The treatment cycle was repeated every 2 weeks, and patients were assessed for resectability and response to the treatment after 6 cycles. This study was registered with UMIN Clinical Trial Registry (UMIN000016630).We enrolled 16 patients with LAPC in this study. At dose level 1, one of 8 patients experienced dose-limiting toxicity (DLT). One of the next 8 patients also experienced DLT at dose level 2. Based on these results, level 2 was considered the recommended dose for this regimen. Pancreatectomy with curative intent could be performed in 13 of the 16 patients. R0 resection was performed in 12 of 13 patients.In conclusion, recommended doses for a biweekly GAS chemotherapy regimen were determined as nab-paclitaxel: 125 mg/m(2), gemcitabine: 1000 mg/m(2) on day 1, S-1: < 1.25 m(2), 60 mg; 1.25-1.5 m(2), 80 mg; > 1.5 m(2), 100 mg twice a day on days 1-7. GAS chemotherapy showed good preliminary efficacy with mild toxicity in this study, and warrants a further phase 2 trial to investigate the efficacy of the GAS regimen for LAPC.