CAJ | 학술논문

目的评价曲妥珠单抗联合化疗治疗人表皮生长因子受体2(HER-2)阳性的耐药晚期胃或胃食管结合部腺癌的疗效和安全性.方法收集北京大学肿瘤医院消化内科2009年6月至2013年8月收治的20例HER-2阳性晚期胃或胃食管结合部腺癌患者的临床资料,患者既往至少接受1种化疗方案进展后,观察曲妥珠单抗联合化疗的疗效和不良反应.结果 20例患者中,曲妥珠单抗联合顺铂或奥沙利铂+氟尿嘧啶9例,联合紫杉醇+氟尿嘧啶5例,联合氟尿嘧啶单药3例,联合伊立替康单药2例,联合多西他赛单药1例.20例患者均可评价疗效,部分缓解3例,疾病稳定10例,疾病进展7例,疾病控制率为65.0％;中位无进展生存时间(PFS)和中位总生存时间(OS)分别为6.1个月(95％ CI为3.0 ～9.2个月)和11.1个月(95％ CI为8.4～13.7个月).曲妥珠单抗的中位应用次数为6.5次,＞6次与≤6次者的中位PFS分别为7.8和3.7个月,中位OS分别为13.8和9.5个月,差异均有统计学意义(均P ＜0.05).全组患者最常见的不良反应为食欲下降、粒细胞减少和乏力,且多为1～2级.全组无治疗相关死亡.在曲妥珠单抗可能相关的不良反应方面,未观察到左心室射血分数值降低≥10％的病例,亦无心脏不良事件发生.结论曲妥珠单抗联合化疗治疗HER-2阳性的耐药晚期胃或胃食管结合部腺癌安全有效,但有必要在前瞻性研究中进行验证.
목적 평개곡타주단항연합화료치료인표피생장인자수체2(HER-2)양성적내약만기위혹위식관결합부선암적료효화안전성.방법 수집북경대학종류의원소화내과2009년6월지2013년8월수치적20례HER-2양성만기위혹위식관결합부선암환자적림상자료,환자기왕지소접수1충화료방안진전후,관찰곡타주단항연합화료적료효화불량반응.결과 20례환자중,곡타주단항연합순박혹오사리박+불뇨밀정9례,연합자삼순+불뇨밀정5례,연합불뇨밀정단약3례,연합이립체강단약2례,연합다서타새단약1례.20례환자균가평개료효,부분완해3례,질병은정10례,질병진전7례,질병공제솔위65.0％;중위무진전생존시간(PFS)화중위총생존시간(OS)분별위6.1개월(95％ CI위3.0 ～9.2개월)화11.1개월(95％ CI위8.4～13.7개월).곡타주단항적중위응용차수위6.5차,＞6차여≤6차자적중위PFS분별위7.8화3.7개월,중위OS분별위13.8화9.5개월,차이균유통계학의의(균P ＜0.05).전조환자최상견적불량반응위식욕하강、립세포감소화핍력,차다위1～2급.전조무치료상관사망.재곡타주단항가능상관적불량반응방면,미관찰도좌심실사혈분수치강저≥10％적병례,역무심장불량사건발생.결론 곡타주단항연합화료치료HER-2양성적내약만기위혹위식관결합부선암안전유효,단유필요재전첨성연구중진행험증.
Objective To evaluate the efficacy and safety of trastuzumab combined with chemotherapy in the treatment for HER-2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma.Methods Twenty consecutive cases of chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma treated in Peking University Cancer Hospital between 2009 June and 2013 August were included in this study.The patients with adenocarcinoma were previously confirmed and were eligible if their tumor showed overexpression of HER-2 + + + by immunohistochemistry or HER-2 gene amplification-positive by FISH,and if they failed to at least one previous chemotherapy.Response and toxicities were evaluated with RECIST 1.0 and CTC AE 3.0 criteria.Results The twenty patients received trastuzumab plus second-or later-line chemotherapy,consisting of nine platinum with fluoropyrimidines,five paclitaxel with fluoropyrimidines,three fluoropyrimidines monotherapy,two irinotecan monotherapy,and one docetaxel monotherapy.In these 20 cases,3 PR (15.0％) and 10 SD (50.0％) were achieved,with a disease control rate of 65.0％.The median PFS was 6.1 months (95％ CI 3.0-9.2) and median OS was 11.1 months (95％ CI 8.4-13.7).The median cycle number of Trastuzumab administration was 6.5.The patients treated with Trastuzumab ≥6 times had a median OS of 13.8 months,significantly longer than that of 9.5 months in the patients treated ＜ 6 times (P ＜ 0.001).The patients treated with Trastuzumab ≥6 times had a median PFS of 7.8 months,significantly longer than that of 3.7 months in patients treated ＜ 6 times (P =0.029).Among the 20 cases,loss of appetite (13 cases of grade 1-2),neutropenia (12 cases of grade 1-2 and 3 cases of grade 3-4) and fatigue (9 cases of grade 1-2 and 3 cases of grade 3-4) were the most frequent adverse events.No cardiac events including asymptomatic decreases in LVEF ≥ 10％ and no treatment-related death were recorded.Conclusions Combination of trastuzumab with chemotherapy is effective and safe in patients with HER2-positive advanced chemo-refractory gastric or gastro-esophageal junction adenocarninoma.However,prospective studies are warranted to further confirm its efficacy and safety.