Kim Mi-Jung, Kong Sun-Young, Nam Byung-Ho, Kim Sohee, Park Young-Iee, Park Sook Ryun
Department of Medical Oncology, Center for Gastric Cancer.
Department of Laboratory Medicine, Center for Diagnostic Oncology.
Pharmacogenet Genomics. 2018 Jan;28(1):23-30. doi: 10.1097/FPC.0000000000000320.
This study investigated the efficacy and safety of S-1 versus capecitabine in elderly patients with metastatic gastric cancer (MGC), and examined the association between cytochrome P450 2A6 (CYP2A6) polymorphisms and treatment outcomes.
MGC patients 70-85 years old with Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or 65-70 years old with ECOG PS 2 were randomized to receive S-1 40 mg/m, twice daily, or capecitabine 1250 mg/m, twice daily, on days 1-14 every 3 weeks.
From May 2007 up to July 2010, 107 patients were enrolled. G3/4 neutropenia developed in 3.8% of each arm, and the most common G3/4 nonhematological toxicities were anorexia and fatigue. Vomiting and tearing were more frequent with S-1 and hand-foot syndrome with capecitabine. The primary endpoint, the overall response rate, was 26.4% (14/53, 95% confidence interval: 14.5-38.3%) in S-1 and 24.1% (13/54, 95% confidence interval: 12.7-35.5%) in capecitabine, both of which exceeded the null hypothesis response rate of 10%. The median time to progression (TTP; 3.2 vs. 3.4 months, P=0.813) and overall survival (OS; 8.5 vs. 10.3 months, P=0.691) were similar in both arms. CYP2A6 polymorphisms were associated with S-1 efficacy. In the S-1 arm only, patients with CYP2A6 variant/variant alleles had worse TTP and OS than those with wild/wild or wild/variant alleles, and in multivariate analysis, the CYP2A6 genotype was predictive for TTP and OS.
Both S-1 and capecitabine were active and tolerable for elderly MGC patients. The CYP2A6 genotyping might guide treatment selection.
本研究调查了S-1与卡培他滨在老年转移性胃癌（MGC）患者中的疗效和安全性，并研究了细胞色素P450 2A6（CYP2A6）基因多态性与治疗结果之间的关联。
年龄在70 - 85岁、东部肿瘤协作组（ECOG）体能状态为0 - 2的MGC患者，或年龄在65 - 70岁、ECOG体能状态为2的患者，每3周在第1 - 14天随机接受S-1 40mg/m²，每日2次，或卡培他滨1250mg/m²，每日2次。
从2007年5月至2010年7月，共纳入107例患者。每组中3.8%的患者发生3/4级中性粒细胞减少，最常见的3/4级非血液学毒性为厌食和疲劳。S-1组呕吐和流泪更常见，卡培他滨组手足综合征更常见。主要终点，总缓解率，S-1组为26.4%（14/53，95%置信区间：14.5 - 38.3%），卡培他滨组为24.1%（13/54，95%置信区间：12.7 - 35.5%），两者均超过无效假设缓解率10%。两组的中位疾病进展时间（TTP；3.2对3.4个月，P = 0.813）和总生存期（OS；8.5对10.3个月，P = 0.691）相似。CYP2A6基因多态性与S-1的疗效相关。仅在S-1组中，携带CYP2A6变异/变异等位基因的患者的TTP和OS比携带野生/野生或野生/变异等位基因的患者差，多因素分析显示，CYP2A6基因型可预测TTP和OS。
S-1和卡培他滨对老年MGC患者均有活性且耐受性良好。CYP2A6基因分型可能有助于指导治疗选择。
