ASCO GI 2015：S-1/顺铂可作为晚期胃癌新辅助化疗方案（COMPASS研究）？

2015年ASCO GI研讨会于1月15日～17日在美国旧金山举行。根据经验即使将S-1作为辅助化疗，III期胃癌预后并不尽如人意。新辅助化疗是一种很有希望的方法，但是它的最佳治疗维持时间和方案尚未确定。在此次会议上，研究人员进行了一项II期试验对局部可切除晚期胃癌的新辅助化疗方案进行比较（COMPASS生存期结果分析）。

研究方法

研究人员开展了一项随机II期试验，利用一种2×2析因设计，对S-1/顺铂（SC）或者紫杉醇/顺铂（PC）的2个或者4个疗程和方案进行了比较。关键的符合标准是：（i）在硬癌和交界肿瘤病例中T2-3/N+或者T4aN0，主要分支动脉T2-3伴有N+，T4aN+，T4b，主动脉旁淋巴结转移，或者通过腹腔镜检查确认可切除最小腹膜转移，以及（ii）没有其他远端转移。

患者们接受S-1（80mg/m2，维持21天，休息1周）/顺铂（60mg/m2，在第8天）或者紫杉醇/顺铂（分别为80mg/m2和25mg/m2，在第1，8和15天，休息1周）作为新辅助化疗。然后，患者以治愈为目的接受D2胃切除术。主要终点是3年总生存期。

研究结果

83例患者被分配到SC组（n=41，两个疗程组：21名；四个疗程组：20名）和PC组（n=42，两个疗程组：21名；四个疗程组：21名）。病理缓解率在SC组是42%（17/42），PC组为33%（14/42），两个疗程组为36%（15/42），四个疗程组是39%（16/41）。病理CR，在两个疗程组为0%（0/42），四个疗程组是10%（4/41）。

由化疗引起的3/4级不良事件和根据Clavien-Dindo分类定义的3/4级手术并发症在每一个组均低于10%，没有治疗相关的死亡。

此外，3年总生存期分别为，SC组是60.9%（95% CI，44.3～73.9%），PC组为64.3%（95% CI，47.9～76.7%），两个疗程组是64.3%（95% CI，47.9～76.7%），四个疗程组为61.0%（95% CI，44.4～74.0%）。

研究结论

S-1/顺铂的两个疗程治疗方案，作为新辅助化疗，是可以推荐作为局部可切除晚期胃癌患者下一步III期研究的一个试验组。临床试验信息：UMIN000002595。
英文摘要：

A randomized 2×2 phase II trial comparing two and four courses of S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) as neoadjuvant chemotherapy for locally resectable advanced gastric cancer: Survival results of COMPASS.（Abstract111）

Background：The prognosis for stage III gastric cancer is not satisfactory even by S-1 adjuvant chemotherapy. Neoadjuvant chemotherapy is a promising approach but its optimal duration and regimen have not been established yet. 

Methods：We conducted a randomized phase II trial to compare two or four courses and regimen of SC or PC using a two-by-two factorial design.Key eligibility criteria was (i) T2-3/N+ or T4aN0 in case of schirrhous or junctional tumors, T2-3 with N+ to the major branched artery, T4aN+, T4b, para-aortic nodal metastases, or resectable minimal peritoneal metastases confirmed by laparoscopy and (ii) no other distant metastasis. Patients received S-1 (80 mg/m2 for 21 days with 1 week rest) / cisplatin (60 mg/m2 at day 8) or paclitaxel / cisplatin (80 mg/m2 and 25 mg/m2, respectively, on days 1, 8, and 15 with 1 week rest) as neoadjuvant chemotherapy. Then, patients received D2 gastrectomy with curative intent. The primary endpoint was 3-year overall survival. The planned sample size was 80 eligible patients in total so that the treatment group with the superior observed 3-year OS rate by 10% increase was to be selected with a probability of 88% or higher. 

Results：Eighty-three patients were assigned to SC (n=41, two courses in 21 and four courses in 20) and PC (n=42, two courses in 21 and four courses in 21). Pathological response rate was 42% (17/41) in SC and 33% (14/42) in PC, and 36% (15/42) in the two courses and 39% (16/41) in the four courses. Pathological CR was 0% (0/42) in the two courses and 10% (4/41) in the four courses. Grade 3/4 adverse events by chemotherapy and grade 3/4 surgical morbidities defined by Clavien-Dindo classification were both less than 10% in each arm without treatment-related death. The 3-year OS was 60.9% (95% CI, 44.3-73.9%) in SC and 64.3% (95% CI, 47.9-76.7%) in PC, and 64.3% (95% CI, 47.9-76.7%) in the two courses and 61.0% (95% CI, 44.4-74.0%) in the four courses. 

Conclusions：Two courses of SC as neoadjuvant chemotherapy is recommended for a test arm of future phase III study for patients with locally resectable advanced gastric cancer. Clinical trial information: UMIN000002595.