2015年ASCO GI研討會(huì)于1月15日——17日在美國舊金山舉行。根據(jù)經(jīng)驗(yàn)即使將S-1作為輔助化療，III期胃癌預(yù)后并不盡如人意。新輔助化療是一種很有希望的方法，但是它的最佳治療維持時(shí)間和方案尚未確定。在此次會(huì)議上，研究人員進(jìn)行了一項(xiàng)II期試驗(yàn)對(duì)局部可切除晚期胃癌的新輔助化療方案進(jìn)行比較（COMPASS生存期結(jié)果分析）。

    研究方法

    研究人員開展了一項(xiàng)隨機(jī)II期試驗(yàn)，利用一種2×2析因設(shè)計(jì)，對(duì)S-1/順鉑（SC）或者紫杉醇/順鉑（PC）的2個(gè)或者4個(gè)療程和方案進(jìn)行了比較。關(guān)鍵的符合標(biāo)準(zhǔn)是：（i）在硬癌和交界腫瘤病例中T2-3/N+或者T4aN0,主要分支動(dòng)脈T2-3伴有N+,T4aN+,T4b,主動(dòng)脈旁淋巴結(jié)轉(zhuǎn)移，或者通過腹腔鏡檢查確認(rèn)可切除最小腹膜轉(zhuǎn)移，以及（ii）沒有其他遠(yuǎn)端轉(zhuǎn)移。

    患者們接受S-1（80mg/m2,維持21天，休息1周）/順鉑（60mg/m2,在第8天）或者紫杉醇/順鉑（分別為80mg/m2和25mg/m2,在第1,8和15天，休息1周）作為新輔助化療。然后，患者以治愈為目的接受D2胃切除術(shù)。主要終點(diǎn)是3年總生存期。

    研究結(jié)果

    83例患者被分配到SC組（n=41,兩個(gè)療程組：21名；四個(gè)療程組：20名）和PC組（n=42,兩個(gè)療程組：21名；四個(gè)療程組：21名）。病理緩解率在SC組是42%（17/42），PC組為33%（14/42），兩個(gè)療程組為36%（15/42），四個(gè)療程組是39%（16/41）。病理CR,在兩個(gè)療程組為0%（0/42），四個(gè)療程組是10%（4/41）。

    由化療引起的3/4級(jí)不良事件和根據(jù)Clavien-Dindo分類定義的3/4級(jí)手術(shù)并發(fā)癥在每一個(gè)組均低于10%,沒有治療相關(guān)的死亡。

    此外，3年總生存期分別為，SC組是60.9%（95% CI,44.3——73.9%），PC組為64.3%（95% CI,47.9——76.7%），兩個(gè)療程組是64.3%（95% CI,47.9——76.7%），四個(gè)療程組為61.0%（95% CI,44.4——74.0%）。

    研究結(jié)論

    S-1/順鉑的兩個(gè)療程治療方案，作為新輔助化療，是可以推薦作為局部可切除晚期胃癌患者下一步III期研究的一個(gè)試驗(yàn)組。臨床試驗(yàn)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 ***rmation: UMIN000002595.