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卵巢癌的腹腔热灌注化疗
Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer


Willemien J. van Driel ... 肿瘤 妇产科和儿科 • 2018.01.18
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腹腔热灌注化疗联合细胞减灭术有望成为晚期卵巢癌的一线治疗方案

 

林仲秋†,杨贤子‡,崔书中‡*

† 中山大学孙逸仙纪念医院妇科肿瘤专科;‡ 广州医科大学附属肿瘤医院腹部综合科

* 通讯作者

 

基于美国妇科肿瘤组(GOG)-172试验结果,细胞减灭术(cytoreductive surgery,CRS)辅以腹腔化疗成为晚期卵巢癌的推荐治疗方案(Ⅰ类证据)1。但腹腔内化疗引起的导管相关并发症、对该化疗方式不耐受等问题限制了该方案在临床上广泛推广和应用2

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摘要


背景

新诊断的晚期卵巢癌的治疗通常包括肿瘤细胞减灭术和全身化疗。本试验旨在探索中间性细胞减灭术(interval cytoreductive surgery)中加腹腔内热灌注化疗(HIPEC)能否改善接受新辅助化疗的Ⅲ期上皮性卵巢癌患者的结局。

 

方法

在一项多中心、开放标签的3期临床试验中,我们随机分配245例患者接受中间性肿瘤细胞减灭术联合或不联合顺铂的HIPEC(100 mg/m2),上述患者经3个周期卡铂(曲线下面积,5~6 mg/[mL·min])和紫杉醇(175 mg/m2体表面积)治疗后至少达到疾病稳定。在认为以下手术可行的情况下,手术时对患者进行随机分组:手术后无可见病灶(完全细胞减灭)或者手术后仅有一个或多个直径≤10 mm的残余肿瘤(满意细胞减灭)。术后再进行3个周期的卡铂和紫杉醇治疗。研究主要终点是无复发生存期。关键的次要终点为总生存期和副作用。

 

结果

在意向性治疗分析中,110/123例(89%)接受细胞减灭术不联合HIPEC(手术组)的患者及99/122例(81%)接受细胞减灭术联合HIPEC(手术+HIPEC组)的患者发生了疾病复发或死亡(疾病复发或死亡风险比[HR],0.66;95%置信区间[CI],0.50~0.87;P=0.003)。手术组的中位无复发生存期为10.7个月,手术+HIPEC组的中位无复发生存期为14.2个月。中位随访4.7年时,手术组及手术+HIPEC组分别有76例(62%)和61例(50%)患者死亡(HR=0.67;95% CI,0.48~0.94;P=0.02)。手术组的中位总生存期为33.9个月,手术+HIPEC组的中位总生存期为45.7个月。两组中发生3或4级不良事件的患者比例相似(手术组为25%,手术+HIPEC组为27%,P=0.76)。

 

结论

在Ⅲ期上皮性卵巢癌患者中,在中间性肿瘤细胞减灭术中加入HIPEC比单纯手术获得了更长的无复发生存期和总生存期,且并未导致更高的副作用发生率(由荷兰癌症学会[Dutch Cancer Society]资助;ClinicalTrials.gov注册号为NCT00426257;EudraCT注册号为2006-003466-34)。





作者信息

Willemien J. van Driel, M.D., Ph.D., Simone N. Koole, M.D., Karolina Sikorska, Ph.D., Jules H. Schagen van Leeuwen, M.D., Ph.D., Henk W.R. Schreuder, M.D., Ph.D., Ralph H.M. Hermans, M.D., Ph.D., Ignace H.J.T. de Hingh, M.D., Ph.D., Jacobus van der Velden, M.D., Ph.D., Henriëtte J. Arts, M.D., Ph.D., Leon F.A.G. Massuger, M.D., Ph.D., Arend G.J. Aalbers, M.D., Victor J. Verwaal, M.D., Ph.D., Jacobien M. Kieffer, Ph.D., Koen K. Van de Vijver, M.D., Ph.D., Harm van Tinteren, Ph.D., Neil K. Aaronson, Ph.D., and Gabe S. Sonke, M.D., Ph.D.
From the Departments of Gynecology (W.J.D., S.N.K.), Biometrics (K.S., H.T.), Surgical Oncology (A.G.J.A.), Pathology (K.K.V.V.), and Medical Oncology (S.N.K., G.S.S.) and the Division of Psychosocial Research and Epidemiology (J.M.K., N.K.A.), the Netherlands Cancer Institute, Amsterdam, the Center for Gynecologic Oncology Amsterdam, Amsterdam (W.J.D., S.N.K., J.V.), the Dutch Gynecologic Oncology Group (W.J.D., J.H.S.L., H.W.R.S., R.H.M.H., J.V., H.J.A., L.F.A.G.M., G.S.S.), the Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam (J.V.), the Department of Obstetrics and Gynecology, Sint Antonius Hospital, Nieuwegein (J.H.S.L.), the Department of Gynecologic Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht (H.W.R.S.), the Departments of Gynecology and Obstetrics (R.H.M.H.) and Surgery (I.H.J.T.H.), Catharina Hospital, Eindhoven, the Dutch Peritoneal Oncology Group (I.H.J.T.H., A.G.J.A.), the Department of Gynecologic Oncology, University of Groningen, University Medical Center Groningen, Groningen (H.J.A.), and the Department of Gynecologic Oncology, Radboud University Medical Center, Nijmegen (L.F.A.G.M.) — all in the Netherlands; and the Department of Surgery, Aarhus University Hospital, Aarhus, Denmark (V.J.V.). Address reprint requests to Dr. van Driel at the Department of Gynecology, U1-14 the Netherlands Cancer Institute, 1006 BE Amsterdam, the Netherlands, or at w.v.driel@nki.nl.

 

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