吉西他滨/纳米白蛋白结合型紫杉醇/S-1（GAS）联合新辅助化疗用于局部晚期胰腺腺癌患者的1期研究
A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma.
作者信息
Kondo Naru, Murakami Yoshiaki, Uemura Kenichiro, Sudo Takeshi, Hashimoto Yasushi, Nakagawa Naoya, Takahashi Shinya, Ohge Hiroki, Sueda Taijiro
机构信息
Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Department of Surgery, Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
出版信息
Cancer Chemother Pharmacol. 2017 Apr;79(4):775-781. doi: 10.1007/s00280-017-3274-0. Epub 2017 Mar 14.
PURPOSE
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).
METHODS
Patients with borderline resectable or unresectable LAPC without distant metastasis were eligible for this study. The planned dosages of gemcitabine (mg/m, day 1), nab-paclitaxel (mg/m, 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).
RESULTS
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.
CONCLUSION
In conclusion, recommended doses for a biweekly GAS chemotherapy regimen were determined as nab-paclitaxel: 125 mg/m, gemcitabine: 1000 mg/m on day 1, S-1: <1.25 m, 60 mg; 1.25-1.5 m, 80 mg; >1.5 m, 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.
目的
确定用于局部晚期胰腺导管腺癌（LAPC）患者的每两周一次的吉西他滨、白蛋白结合型紫杉醇和S-1（GAS）联合新辅助化疗的推荐剂量。
方法
无远处转移的可切除边缘或不可切除的LAPC患者符合本研究条件。吉西他滨（mg/m²，第1天）、白蛋白结合型紫杉醇（mg/m²，第1天）和S-1（mg/天，第1 - 7天）的计划剂量在1级为800/100/60 - 100，在2级为1000/125/60 - 100。治疗周期每2周重复一次，6个周期后评估患者的可切除性和对治疗的反应。本研究已在UMIN临床试验注册中心注册（UMIN000016630）。
结果
本研究纳入了16例LAPC患者。在1级剂量水平，8例患者中有1例出现剂量限制性毒性（DLT）。接下来的8例患者中有1例在2级剂量水平也出现了DLT。基于这些结果，2级被认为是该方案的推荐剂量。16例患者中有13例可以进行根治性胰腺切除术。13例患者中有12例进行了R0切除。
结论
总之，每两周一次的GAS化疗方案的推荐剂量确定为：白蛋白结合型紫杉醇：125 mg/m²，吉西他滨：第1天1000 mg/m²，S-1：<1.25 m²，60 mg；1.25 - 1.5 m²，80 mg；>1.5 m²，100 mg，第1 - 7天每天两次。本研究中GAS化疗显示出良好的初步疗效且毒性轻微，值得进一步进行2期试验以研究GAS方案对LAPC的疗效。
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