近日,，發(fā)表于Lancet的一項(xiàng)亞洲研究表明，對(duì)于可手術(shù)的胃癌病人,，使用卡倍他濱和奧沙利鉑的輔助化療應(yīng)該被視為新的治療方案,。 在一個(gè)III期臨床試驗(yàn)中，他們發(fā)現(xiàn)D2胃癌手術(shù)切除術(shù)后進(jìn)行6個(gè)月的聯(lián)合化療,，與單獨(dú)手術(shù)相比,，可提高3年無(wú)疾病生存期（74% vs 59%；HR, 0.56,；P < 0.0001） ,。
然而,，化療帶來(lái)的療效伴隨著3或4級(jí)不良事件的高發(fā)生率 （56%）。研究納入了1035名II到IIIB期胃癌患者,，涉及37個(gè)臨床中心,，多數(shù)在韓國(guó)，這項(xiàng)試驗(yàn)被稱(chēng)為胃癌患者卡倍他濱和奧沙利鉑輔助化療研究（CLASSIC）,。
這項(xiàng)臨床試驗(yàn)因?yàn)槠滹@示的效益已被終止,。中期療效分析的結(jié)果發(fā)表在1月28日的柳葉刀雜志上。研究者Yung-Jue Bang 寫(xiě)到,，這項(xiàng)發(fā)現(xiàn)可能也適用于D2手術(shù)后的其他部位,。
然而，在同期述評(píng)中,，一位來(lái)自日本的專(zhuān)家Toshirou Nishida對(duì)這項(xiàng)結(jié)果的普遍性提出了質(zhì)疑,。他寫(xiě)到，在亞洲,，我們有2種輔助治療的選擇,，這兩項(xiàng)選擇是卡倍他濱聯(lián)合奧沙利鉑，和口服氟尿嘧啶類(lèi)藥物S-1,，該輔助治療已經(jīng)在胃癌患者TS-1輔助化療試驗(yàn)（ACTS-GS）中進(jìn)行了研究,。Nishida沒(méi)有說(shuō)非亞洲國(guó)家也有兩種選擇，說(shuō)明一個(gè)病人所在的國(guó)家對(duì)癌癥治療有重要的影響,。
Nishida博士寫(xiě)到,，輔助治療是用來(lái)消除根治術(shù)后潛在的微轉(zhuǎn)移，治療策略的選擇依賴(lài)于術(shù)后預(yù)期的局部疾病控制,、治療機(jī)構(gòu)和國(guó)家,。在亞洲，D2胃切除術(shù)是標(biāo)準(zhǔn)治療,，全身輔助化療已經(jīng)是常規(guī),，主要是因?yàn)锳CTS-GS的早期結(jié)果。在非亞洲國(guó)家,，D1手術(shù)指最常見(jiàn)的手術(shù),。
該研究的作者也探討了普遍性的問(wèn)題。他們承認(rèn)他們的研究人群比起歐洲和美國(guó)的胃癌研究人群,，具有較少的晚期疾?。═3和T4病變），西方研究中的人群歷來(lái)比亞洲的生存結(jié)局要壞,。但作者認(rèn)為,，研究得出的比較好的結(jié)局并不是因?yàn)槿巳壕哂休^少的晚期疾病。這項(xiàng)好的結(jié)果是因?yàn)橐回炇褂肈2手術(shù)而且手術(shù)質(zhì)量高的原因,。他們建議到,，非亞洲國(guó)家也可以做高質(zhì)量的D2手術(shù),。畢竟，D2胃切除術(shù)在歐洲和美國(guó)都是標(biāo)準(zhǔn)治療,。但是作者沒(méi)有討論過(guò)標(biāo)準(zhǔn)治療和實(shí)際治療可能存在的潛在差異,。
胃癌治療的安全性和依從性問(wèn)題
在CLASSIC試驗(yàn)中，經(jīng)歷D2胃切除術(shù)的病人被隨機(jī)分配到化療組或單獨(dú)手術(shù)組,，化療組中,，有8個(gè)三周的循環(huán)，口服卡倍他濱（1000 mg/m^2,，每個(gè)循環(huán)的第1~14天,，每天2次），加上靜脈注射奧沙利鉑（130 mg/m^2,每個(gè)循環(huán)的第1天）,，持續(xù)6個(gè)月,。
研究結(jié)果產(chǎn)生了一個(gè)簡(jiǎn)單的問(wèn)題，Nishida博士提出：所有可手術(shù)的胃癌病人都應(yīng)該在術(shù)后進(jìn)行化療嗎,？這個(gè)不是簡(jiǎn)單能夠回答的,。病人和醫(yī)生應(yīng)該權(quán)衡復(fù)發(fā)風(fēng)險(xiǎn)，治療負(fù)擔(dān)包括不良事件,、花費(fèi),，以及治療的療效，然后做出決定,。有相當(dāng)比例的病人通過(guò)手術(shù)就可達(dá)到治愈,。
在對(duì)CLASSIC的評(píng)論中，Nishida博士強(qiáng)調(diào)了化療組的不良事件,，最常見(jiàn)的是惡心（n=326）,，中性粒細(xì)胞減少（n=300），食欲下降（n=294）,?；熃M有超過(guò)一半的人群經(jīng)歷3或4級(jí)的不良事件，近10%因?yàn)椴涣际录顺鲋委?，從治療中退出的總?cè)藬?shù)更多，達(dá)到33%,。
卡倍他濱+奧沙利鉑的總體生存效益還未確定,，確定下來(lái)至少需要5年的隨訪。（生物谷Bioon.com）
doi:10.1016/S0140-6736(11)61873-4
PMC:
PMID:
Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial
Yung-Jue Bang, Young-Woo Kim, Han-Kwang Yang, Hyun Cheol Chung, Young-Kyu Park, Kyung Hee Lee, Keun-Wook Lee, Yong Ho Kim, Sang-Ik Noh, Jae Yong Cho, Young Jae Mok, Yeul Hong Kim, Jiafu Ji, Ta-Sen Yeh, Peter Button, Florin Sirzén, Sung Hoon Noh
Background
D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II—IIIB gastric cancer.
Methods
The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II—IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m2 twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m2 on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov (NCT00411229).
Findings
1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4—41·7) in the chemotherapy and surgery group and 34·3 months (25·6—41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69—79) in the chemotherapy and surgery group and 59% (53—64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44—0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294).
Interpretation
Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer.
Funding
F Hoffmann-La Roche and Sanofi-Aventis.
