吉西他滨、S-1与亚叶酸联合（GSL）疗法用于晚期胰腺癌的I期试验。
A phase I trial of gemcitabine, S-1 and LV combination (GSL) therapy in advanced pancreatic cancer.
作者信息
Nakai Yousuke, Isayama Hiroyuki, Saito Kei, Sasaki Takashi, Takahara Naminatsu, Hamada Tsuyoshi, Mizuno Suguru, Miyabayashi Koji, Yamamoto Keisuke, Mohri Dai, Kogure Hirofumi, Yamamoto Natsuyo, Hirano Kenji, Ijichi Hideaki, Tateishi Keisuke, Tada Minoru, Koike Kazuhiko
机构信息
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan.
出版信息
Cancer Chemother Pharmacol. 2014 Nov;74(5):911-5. doi: 10.1007/s00280-014-2563-0. Epub 2014 Aug 21.
PURPOSE
In our previous randomized controlled trial, the addition of S-1 to gemcitabine for advanced pancreatic cancer did not prolong overall survival (OS) significantly, despite its higher response rate and longer progression-free survival (PFS). Leucovorin is known to enhance efficacy of S-1, and we conducted this phase I trial of combination therapy of gemcitabine, S-1 and leucovorin (GSL).
METHODS
Patients with advanced pancreatic cancer who had received no prior chemotherapy were eligible for this study. Gemcitabine was administered at an escalating dose of 600, 800 and 1,000 mg/m(2) over 30 min on day 1, and oral S-1 at a dose of 40 mg/m(2) twice daily and oral leucovorin at a dose of 25 mg twice daily on days 1-7, every 2 weeks. A standard "3 + 3" phase I dose escalation design was utilized.
RESULTS
Fifteen patients were enrolled across three dose levels. Three patients developed DLTs: two patients in level 1 (grade 3 anorexia in 1 and grade 3 anorexia, stomatitis and diarrhea in 1) and one patient in level 2 (grade 3 deep vein thrombosis). No DLT was observed in level 3. Response rate and the disease control rate were 33 and 93 %, respectively. The median PFS and OS were 5.4 and 16.6 months. Ten of 12 patients (83 %) with elevated CA19-9 at baseline had a ≥ 50 % decline.
CONCLUSIONS
RD of gemcitabine in GSL was determined as 1,000 mg/m(2). GSL was well tolerable and showed promising results in advanced pancreatic cancer.
目的
在我们之前的随机对照试验中，对于晚期胰腺癌患者，在吉西他滨基础上加用S-1尽管有更高的缓解率和更长的无进展生存期（PFS），但并未显著延长总生存期（OS）。已知亚叶酸可增强S-1的疗效，因此我们开展了这项吉西他滨、S-1和亚叶酸联合治疗（GSL）的I期试验。
方法
未接受过化疗的晚期胰腺癌患者符合本研究条件。吉西他滨在第1天30分钟内按600、800和1000mg/m²的剂量递增给药，口服S-1剂量为40mg/m²，每日两次，口服亚叶酸剂量为25mg，每日两次，于第1 - 7天给药，每2周重复。采用标准的“3 + 3”I期剂量递增设计。
结果
15例患者入组三个剂量水平。3例患者出现剂量限制性毒性（DLT）：1级2例（1例3级厌食，1例3级厌食、口腔炎和腹泻），2级1例（3级深静脉血栓形成）。3级未观察到DLT。缓解率和疾病控制率分别为33%和93%。中位PFS和OS分别为5.4个月和16.6个月。12例基线CA19-9升高的患者中有10例（83%）下降≥50%。
结论
GSL中吉西他滨的推荐剂量（RD）确定为1000mg/m²。GSL耐受性良好，在晚期胰腺癌中显示出有前景的结果。
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