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上皮性卵巢癌周剂量密集化疗并不能延长无进展生存期
作者:小柯机器人 发布时间:2019/12/6 15:25:52

英国伦敦大学学院Elizabeth C James研究组宣布,他们的最新研究分析了在上皮性卵巢、输卵管或原发性腹膜癌的一线治疗中,周剂量密集化疗的无进展生存结果。相关论文2019年11月29日发表在《柳叶刀》上。

每3周给药一次卡铂和紫杉醇,是一线治疗上皮性卵巢癌的标准化疗方案。日本JGOG3016试验表明,每周一次紫杉醇和每3周一次卡铂,可显著改善无进展生存和总生存期。

2011年6月6日至2014年11月28日,研究组在欧洲进行了一项临床3期的随机对照试验,招募了1566名新诊断为上皮性卵巢癌的女性,均为国际妇产科联合会IC-IV期。将其随机分为3组,第1组接受每3周一次卡铂+紫杉醇,第2组接受每3周一次卡铂+每周一次紫杉醇,第3组接受每周一次卡铂+紫杉醇。参与者均签署了知情同意书,并获得研究地国家伦理委员会的批准。

虽然三组中分别有90%、89%和85%的患者完成了6个疗程的铂类化疗,但仅有72%、60%和63%的患者完成了6个疗程的试验化疗方案。每周化疗一次,紫杉醇的用量显著增加。截至2017年3月,共有1018名患者(65%)发生疾病进展。

第1组的限制平均生存时间为24.4个月,第2组为24.9个月,第3组为25.3个月。第1组的中位无进展生存期为17.7个月,第2组为20.8个月,第3组为21.0个月,但三组间差异不显著。每周化疗增加了3或4级毒副作用,但均不严重。三组间发热性中性粒细胞减少和感觉神经病变的发生率相差不大。

总之,周剂量密集化疗可用于上皮性卵巢癌的一线化疗,但与欧洲主要人群每3周一次的标准化疗方案相比,并未能显著提高无进展生存率。

附:英文原文

Title: Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial

Author: Andrew R Clamp, Elizabeth C James, Iain A McNeish, Andrew Dean, Jae-Weon Kim, Dearbhaile M ODonnell, Jane Hook, Christopher Coyle, Sarah Blagden, James D Brenton, Raj Naik, Tim Perren, Sudha Sundar, Adrian D Cook, Gosala S Gopalakrishnan, Hani Gabra, Rosemary Lord, Graham Dark, Helena M Earl, Marcia Hall, Susana Banerjee, Rosalind M Glasspool, Rachel Jones, Sarah Williams, Ann Marie Swart, Sally Stenning, Mahesh Parmar, Richard Kaplan, Jonathan A Ledermann

Issue&Volume: November 29, 2019

Abstract:

Background

Carboplatin and paclitaxel administered every 3 weeks is standard-of-care first-line chemotherapy for epithelial ovarian cancer. The Japanese JGOG3016 trial showed a significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly carboplatin. In this study, we aimed to compare efficacy and safety of two dose-dense weekly regimens to standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer.

Methods

In this phase 3 trial, women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC–IV epithelial ovarian cancer were randomly assigned to group 1 (carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m2 paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m2 paclitaxel weekly), or group 3 (carboplatin AUC2 and 80 mg/m2 paclitaxel weekly). Written informed consent was provided by all women who entered the trial. The protocol had the appropriate national research ethics committee approval for the countries where the study was conducted. Patients entered the trial after immediate primary surgery, or before neoadjuvant chemotherapy with subsequent planned delayed primary surgery. The trial coprimary outcomes were progression-free survival and overall survival. Data analyses were done on an intention-to-treat basis, and were powered to detect a hazard ratio of 0·75 in progression-free survival. The main comparisons were between the control group (group 1) and each of the weekly research groups (groups 2 and 3).

Findings

Between June 6, 2011, and Nov 28, 2014, 1566 women were randomly assigned to treatment. 72% (365), completed six protocol-defined treatment cycles in group 1, 60% (305) in group 2, and 63% (322) in group 3, although 90% (454), 89% (454), and 85% (437) completed six platinum-based chemotherapy cycles, respectively. Paclitaxel dose intensification was achieved with weekly treatment (median total paclitaxel dose 1010 mg/m2 in group 1; 1233 mg/m2 in group 2; 1274 mg/m2 in group 3). By February, 2017, 1018 (65%) patients had experienced disease progression. No significant progression-free survival increase was observed with either weekly regimen (restricted mean survival time 24·4 months [97·5% CI 23·0–26·0] in group 1, 24·9 months [24·0–25·9] in group 2, 25·3 months [23·9–26·9] in group 3; median progression-free survival 17·7 months [IQR 10·6–not reached] in group 1, 20·8 months [11·9–59·0] in group 2, 21·0 months [12·0–54·0] in group 3; log-rank p=0·35 for group 2 vs group 1; group 3 vs 1 p=0·51). Although grade 3 or 4 toxic effects increased with weekly treatment, these effects were predominantly uncomplicated. Febrile neutropenia and sensory neuropathy incidences were similar across groups.

Interpretation

Weekly dose-dense chemotherapy can be delivered successfully as first-line treatment for epithelial ovarian cancer but does not significantly improve progression-free survival compared with standard 3-weekly chemotherapy in predominantly European populations.

DOI: 10.1016/S0140-6736(19)32259-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32259-7/fulltext

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
官方网址:http://www.thelancet.com/
投稿链接:http://ees.elsevier.com/thelancet