From the Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre, University of Melbourne (T.L., M.M., W.K.M.), the School of Public Health, Monash University (J.Z.), the Department of Medical Oncology, Alfred Health (J.Z.), Central Clinical School, Alfred Centre (A.B.), and Monash Medical Centre (A.S.), Melbourne, VIC, Princess Alexandra Hospital, University of Queensland, Brisbane (B.M.S.), and Cancer Care Services, Sunshine Coast University Hospital, Birtinya, QLD (D.W.), National Health and Medical Research Council Clinical Trials Centre, University of Sydney (V.G., R.L.O., J.S.), and Chris O'Brien Lifehouse (D.M.), Sydney, and the Trans-Tasman Radiation Oncology Group, University of Newcastle, Newcastle, NSW (A.M.) - all in Australia; the Department of Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium (K.H.); Princess Margaret Hospital (R.W.) and Mount Sinai Hospital (C.S.), Toronto, the Canadian Cancer Trials Group, Queen's University, Kingston, ON (C.O.), Nova Scotia Health Central Zone, Halifax (G.D.), and Centre Hospitalier de l'Université de Montréal, Montreal (M.L.) - all in Canada; the Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (M.F.); University Cancer Center Leipzig and Comprehensive Cancer Center Central Germany Leipzig-Jena, University Medicine Leipzig, Leipzig, Germany (F.L.); and Sainte Catherine Institut du Cancer Avignon-Provence, Avignon, France (L.M.).
N Engl J Med. 2024 Nov 14;391(19):1810-1821. doi: 10.1056/NEJMoa2405195. Epub 2024 Sep 14.
In Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone.
We conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control). In both groups, patients received either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel both before and after surgery; the preoperative-chemoradiotherapy group also received chemoradiotherapy (45 Gy in 25 fractions of radiation, plus fluorouracil infusion). The primary end point was overall survival, and secondary end points included progression-free survival, pathological complete response, toxic effects, and quality of life.
A total of 574 patients underwent randomization at 70 sites in Australasia, Canada, and Europe: 286 to the preoperative-chemoradiotherapy group and 288 to the perioperative-chemotherapy group. A higher percentage of patients in the preoperative-chemoradiotherapy group than in the perioperative-chemotherapy group had a pathological complete response (17% vs. 8%) and greater tumor downstaging after resection. At a median follow-up of 67 months, no significant between-group differences in overall survival or progression-free survival were noted. The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% confidence interval, 0.83 to 1.31), and the median progression-free survival was 31 months and 32 months, respectively. Treatment-related toxic effects were similar in the two groups.
The addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma. (Funded by the National Health and Medical Research Council and others; TOPGEAR ClinicalTrials.gov number, NCT01924819.).
在西方国家，可切除胃癌的标准治疗方法是围手术期化疗。术前放化疗也已被考虑，但与单独围手术期化疗相比，关于这种治疗的数据有限。
我们进行了一项国际性的 3 期临床试验，将可切除的胃腺癌或胃食管交界处腺癌患者随机分为术前放化疗加围手术期化疗组或单独围手术期化疗组（对照组）。两组患者均在术前和术后接受表柔比星、顺铂和氟尿嘧啶或氟尿嘧啶、亚叶酸钙、奥沙利铂和多西他赛治疗；术前放化疗组还接受 45Gy 的 25 次分割放疗和氟尿嘧啶输注。主要终点是总生存期，次要终点包括无进展生存期、病理完全缓解、毒性作用和生活质量。
共有 70 个地点的 574 名患者被随机分配到术前放化疗组和围手术期化疗组：术前放化疗组 286 例，围手术期化疗组 288 例。术前放化疗组病理完全缓解率（17%比 8%）和切除后肿瘤降期比例高于围手术期化疗组。中位随访 67 个月时，两组总生存期和无进展生存期均无显著差异。术前放化疗组的中位总生存期为 46 个月，围手术期化疗组为 49 个月（死亡风险比，1.05；95%置信区间，0.83 至 1.31），中位无进展生存期分别为 31 个月和 32 个月。两组的治疗相关毒性作用相似。
与单独围手术期化疗相比，可切除胃和胃食管交界处腺癌患者术前放化疗联合围手术期化疗并未改善总生存期。（由澳大利亚新西兰卫生与医学研究理事会等资助；TOPGEAR ClinicalTrials.gov 编号，NCT01924819）。
