title: Dose-finding study on adjuvant chemotherapy with S-1 plus oxaliplatin for gastric cancer.
abstract: Gastric cancer (GC) is the fourth most common type of cancer, accounting for an estimated one million new cases annually worldwide. Locally advanced GC often recurs, even following curative surgical resection. Therefore, there is a need for an effective adjuvant chemotherapy regimen. The aim of this trial was to investigate the maximum tolerated dose (MTD) of S-1 when administered in combination with oxaliplatin in postoperative GC patients. Oxaliplatin was administered at a fixed dose of 130 mg/m2on day 1. S-1 was administered from day 1 to 14 of a 3-week cycle and escalated by 10 mg/m2/day from 60 to 80 mg/m2/day. A total of 15 patients were enrolled in this study. No dose-limiting toxicities (DLTs) occurred at level 1 (S-1, 60 mg/m2; n=3). One case of DLT (grade 3 vomiting) occurred at level 2 (S-1, 70 mg/m2; n= 6), whereas 2 cases of grade 3 vomiting were observed at level 3 (S-1, 80 mg/m2; n=6). Based on these results, the MTD of S-1 was initially determined to be 70 mg/m2. Furthermore, we observed that cytochrome P450 2A6 (CYP2A6) 41349640C>G was associated with severe neutropenia (C/C vs. C/G vs. G/G = 0 vs. 33.33 vs. 100%; P=0.03297, Fisher's exact test) during the entire course of the treatment.
authors.affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021;
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021;
authors.forename: Qiong
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021;
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021;
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021;
authors.forename: Jinwan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Shu
authors.affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021;
authors.forename: Xinghua
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
authors.forename: Songnian
authors.initials: S
authors.lastname: Hu
keywords: S-1; adjuvant chemotherapy; cytochrome P450 2A6; maximum-tolerated dose; oxaliplatin