ASCO2013：研究发现S-1联合顺铂一线治疗晚期胃癌或胃食管连接部腺癌安全有效

中山大学徐瑞华等研究发现S-1联合顺铂一线治疗晚期胃癌或胃食管连接部腺癌安全有效
背景：一线治疗晚期胃癌中S-1联合顺铂（DDP）方案已被日本研究者证明是有效和安全的。这是亚洲第一项比较S-1联合顺铂与5-氟尿嘧啶（5-FU）联合顺铂的随机的III期临床试验。
方法：这是一个开放性、多中心、III期随机对照研究。胃或胃食管交界处腺癌患者被纳入其中。患者按1:1的比例被随机分配接受S-1联合顺铂（实验组）或5-氟尿嘧啶联合顺铂（对照组），研究共进行了6个周期。在实验组中，1-21天S-1的剂量为80 mg/m2/天，口服，每日2次；第1-4天顺铂为20 mg/m2/天，每5周重复一次。在对照组中，5-FU为0.8 mg/m2/天CI 120小时，顺铂剂量与实验组相同，每4周重复一次。这种分配采用区组随机化的方式，它是由东部肿瘤协作组根据性能状态、转移和切除前的部位进行分层决定的。该研究的主要终点是疾病进展时间（TTP）。次要终点包括：治疗失败时间（TTF）、总生存率（OS）、生活质量。
结果：共有225例患者被纳入了该研究，对其中的236例进行了分析（n = 120; n = 116）。其中，实验组的中位TTP（95% CI 4.59-6.26）为5.51个月，与之相比，对照组的中位TTP（95% CI 4.00-6.33）为4.62个月（HR为1.03；95% CI 0.76-1.39，P = 0.86）。在实验组和对照组，反应率分别为22.5%、21.5%；P = 0.86。实验组中位OS为10个月（95% CI 8.59-14.52），与之相比，对照组为10.46个月（8.92-13.84）（HR 1.05；95% CI 0.71-1.54，P = 0.82）。两组中最常见的不良反应为：贫血（S-1联合顺铂为80.17%与5-氟尿嘧啶联合顺铂为71.19%）、白细胞减少症（71.90% vs 62.71%）、中性粒细胞减少（68.60% vs 55.93%）、恶心（50.41% vs 60.17%）、血小板减少（44.63% vs 26.27%）、呕吐（42.98% vs 42.37%）、厌食症（38.02% vs 41.53%）。
结论：对胃或胃食管交界处腺癌晚期患者而言，S-1联合顺铂是一种有效且耐受性较好的选择。临床试验信息：NCT01198392.
A phase III study of S-1 plus cisplatin versus fluorouracil plus cisplatin in patients with advanced gastric or gastroesophageal junction adenocarcinoma.
Abstract
Background: A combination of S-1 and cisplatin (DDP) has been shown to be effective and safe for the first-line treatment of advanced gastric cancer in Japan. This is the first randomized phase III trial to compare S-1 plus DDP with 5-fluorouracil (5-Fu) plus DDP in Asia. Methods: This is an open-label, multicenter, phase 3, randomized controlled study. Patients with gastric or gastro-oesophageal junction adenocarcinoma were eligible for inclusion. Patients were randomly assigned in a 1:1 ratio to receive S-1 plus DDP (experiment group) or 5-Fu plus DDP (control group) for 6 cycles. In the experiment group, the dose of S-1 was 80 mg/m2/day, po, twice daily on day 1-21 and DDP was 20mg/m2 iv on day 1-4, repeat every 5 weeks. In the control group, 5-Fu was given as 0.8g/m2/d CI 120h ,and the dose of DDP was the same with the experiment group, while repeat every 4 weeks. Allocation was by block randomization stratified by Eastern Cooperative Oncology Group performance status, sites of metastasis and prior gastrectomy. The primary endpoint was time to progression (TTP). Secondary end points included time to failure (TTF), overall survival (OS), and quality of life. Results: Totally 255 patients were enrolled into the study, of whom 236 were included in the analysis (n=120; n=116). Median TTP was 5.51 months (95% CI 4.59-6.26) in those assigned to experiment group compared with 4.62 months (95% CI 4.00-6.33) in the control group (hazard ratio [HR] 1.03; 95%CI 0.76-1.39, p=0.86). In the experiment and control groups, response rates were 22.5% vs 21.5%; P=0.86. Median OS was 10.00 months (95% CI 8.59-14.52) in the experiment group compared with 10.46 months (8.92-13.84) in the control group (HR 1.05; 95%CI 0.71-1.54, p=0.82). The most common adverse events in both groups were anemia (S-1 plus cisplatin, 80.17% vs 5-Fu plus cisplatin, 71.19%), leukopenia (71.90% vs 62.71%), neutropenia (68.60% vs 55.93%), nausea (50.41% vs 60.17%), thrombocytopenia (44.63% vs 26.27%), vomiting (42.98% vs 42.37%) and anorexia (38.02% vs 41.53%). Conclusions: S-1 plus DDP is an effective and tolerable option for patients with advanced gastric or gastro-oesophageal junction adenocarcinoma. Clinical trial information: NCT01198392.