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Ⅲ期结肠癌的辅助化疗持续时间
Duration of Adjuvant Chemotherapy for Stage III Colon Cancer


Axel Grothey ... 肿瘤 • 2018.03.29
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IDEA:期结肠癌术后辅助化疗新纪元

 

陈功†,薛俊丽‡,李进‡*

†中山大学附属肿瘤医院;‡同济大学附属东方医院

*通讯作者

 

自2004年起,MOSAIC1、NSABPC-072及XELOXA3三个大型研究结果,奠定了奥沙利铂在Ⅲ期结肠癌术后辅助化疗中的地位:为期6个月的氟尿嘧啶/奥沙利铂联合方案(FOLFOX或CAPOX)治疗成为新标准。但具体在临床实践中,由于化疗的毒副反应,主要是奥沙利铂的蓄积性外周神经毒性,仅75%~80%的患者能够完成全部6个月的标准治疗。不少患者的外周神经毒性可能持续到化疗结束后多年,乃至不可逆,严重影响了生活质量。为此,业界开始尝试在最大限度保证疗效不受损的前提下,通过缩短化疗疗程来减少化疗所致毒副反应,改善患者生活质量,同时节约医疗资源、减轻社会经济负担。10年前,临床医师和统计师联合启动了IDEA研究4

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摘要


背景

自2004年起,为期6个月的奥沙利铂+氟嘧啶治疗方案就成为Ⅲ期结肠癌患者的标准辅助治疗。但奥沙利铂会引起蓄积性神经毒性,因此缩短治疗时间应该能够降低毒性作用和医疗费用。

 

方法

我们对6项同时进行的3期随机试验进行了前瞻性预设汇总分析,它们都是非劣效性研究,对比了3个月和6个月的FOLFOX(氟尿嘧啶、亚叶酸和奥沙利铂)或CAPOX(卡培他滨和奥沙利铂)辅助治疗。主要终点是3年无病生存率。若风险比的双侧95%置信区间上限未超过1.12,则判定3个月治疗不劣于6个月治疗。

 

结果

12,834例患者中共3,263例疾病复发或死亡之后,研究未能在总体研究人群中确证3个月治疗不劣于6个月治疗(风险比[HR],1.07;95%置信区间[CI],100~1.15)。CAPOX治疗(HR,0.95;95% CI,0.85~1.06)和FOLFOX治疗(HR,1.16;95% CI,1.06~1.26)缩短时间后,仅前者达到非劣效性标准。一项汇总所有疗法的探索性分析发现:T1、T2或T3及N1期患者的3个月治疗不劣于6个月治疗,3年无病生存率分别为83.1%和83.3%(HR,1.01;95% CI,0.90~1.12);而在T4、N2或T4N2期患者中,6个月治疗的无病生存率优于3个月治疗(64.4% vs. 62.7%)(HR,1.12;95% CI,1.03~1.23;优效性P=0.01)。

 

结论

Ⅲ期结肠癌患者接受FOLFOX或CAPOX辅助治疗时,研究未能在总体研究人群中证实3个月治疗不劣于6个月治疗。但3个月CAPOX治疗的效果与6个月相当,尤其是低危亚组(研究由美国国立癌症研究所等资助)。





作者信息

Axel Grothey, M.D., Alberto F. Sobrero, M.D., Anthony F. Shields, M.D., Ph.D., Takayuki Yoshino, M.D., Ph.D., James Paul, Ph.D., Julien Taieb, M.D., John Souglakos, M.D., Qian Shi, Ph.D., Rachel Kerr, Ph.D., Roberto Labianca, M.D., Jeffrey A. Meyerhardt, M.D., M.P.H., Dewi Vernerey, Ph.D., Takeharu Yamanaka, Ph.D., Ioannis Boukovinas, M.D., Jeffrey P. Meyers, B.S., Lindsay A. Renfro, Ph.D., Donna Niedzwiecki, Ph.D., Toshiaki Watanabe, Ph.D., Valter Torri, M.D., Mark Saunders, M.B., B.S., Ph.D., Daniel J. Sargent, Ph.D., Thierry Andre, M.D., and Timothy Iveson, M.D.
From the Divisions of Medical Oncology (A.G.) and Biomedical Statistics and Informatics (Q.S., J.P.M., L.A.R., D.J.S.), Mayo Clinic, Rochester, MN; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Martino-IST, Genoa (A.F. Sobrero), Ospedale Papa Giovanni XXIII, Bergamo (R.L.), and IRCCS Mario Negri Institute for Pharmacological Research, Milan (V.T.) — all in Italy; Karmanos Cancer Institute, Wayne State University, Detroit (A.F. Shields); National Cancer Center Hospital East, Chiba (T. Yoshino), Yokohama City University School of Medicine, Yokohama (T. Yamanaka), and the University of Tokyo, Tokyo (T.W.) — all in Japan; the Institute of Cancer Sciences, University of Glasgow, Glasgow (J.P.), the University of Oxford, Oxford (R.K.), Christie Hospital, Manchester (M.S.), and University Hospital Southampton, Southampton (T.I.) — all in the United Kingdom; Hôpital Européen Georges-Pompidou, Sorbonne Paris Cite/Paris Descartes University (J.T.), and Saint-Antoine Hospital and Sorbonne Universités, Pierre and Marie Curie University–Paris 6 (T.A.), Paris, and Methodology and Quality of Life Unit, INSERM Unité 1098, Besançon (D.V.) — all in France; the Department of Medical Oncology, University Hospital of Heraklion, Faculty of Medicine, University of Crete, Heraklion (J.S.), and Bioclinic Thessaloniki, Thessaloniki (I.B.) — both in Greece; Dana–Farber Cancer Institute, Boston (J.A.M.); and Duke Cancer Institute, Durham, NC (D.N.). Address reprint requests to Dr. Grothey at the Division of Medical Oncology, Mayo Clinic Rochester, 200 First St. SW, Rochester, MN 55905, or at grothey.axel@mayo.edu. Toshiaki Watanabe, Ph.D., and Daniel J. Sargent, Ph.D., are deceased.

 

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