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阿帕替尼间歇给药与持续给药联合多西他赛作为晚期胃癌或胃食管交界腺癌二线治疗的疗效与安全性：一项随机对照研究

Efficacy and safety of intermittent versus continuous dose apatinib plus docetaxel as second-line therapy in patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma: a randomized controlled study.

作者信息

Yan Ying, Li Huimin, Wu Shusheng, Wang Gang, Luo Huiqin, Niu Jiayu, Cao Lulu, Hu Xiaoxiu, Xu Huijun, Jia Wei, Sun Yubei, Yao Yiwei, Chen Wenju, Ke Lihong, Hu Bing, Ji Chushu, Sun Yancai, Chen Jian, Li Mengge, He Yifu

机构信息

Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

出版信息

Ann Transl Med. 2022 Feb;10(4):205. doi: 10.21037/atm-22-546.

DOI:10.21037/atm-22-546

PMID:35280426

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8908117/

Abstract

BACKGROUND

Previous studies of the second-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJAC) had reported that apatinib combined with chemotherapy improved the treatment outcomes. However, the benefits were sometimes limited due to the tolerance of continuous dose regimen. This randomized controlled study aimed to investigate the efficacy and safety of intermittent or continuous dose apatinib plus docetaxel as a second-line therapy in patients with advanced GC/GEJAC.

METHODS

Advanced GC/GEJAC patients who failed first-line chemotherapy were recruited (enrollment time: from September 15, 2017 to July 21, 2019), and randomly assigned to either the intermittent dose group (IG group) or the continuous dose group (CG group) (1:1 ratio) using the block randomization method. In the IG group, patients received apatinib 500 mg/d for 5 consecutive days then held for 2 days plus docetaxel 60 mg/m q3w, in a 3-week cycle. In the CG group, patients received apatinib 500 mg daily plus docetaxel 60 mg/m q3w, in a 3-week cycle. The progression free survival (PFS) was evaluated every two cycles and follow-ups were performed monthly. The primary endpoint was PFS, and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.

RESULTS

In total, 76 eligible patients were enrolled and randomly assigned (1:1 ratio). The IG group exhibited similar PFS compared to the CG group [median PFS: 3.88 (95% CI: 1.72-6.03) months 3.98 (95% CI: 1.06-6.90) months, P=0.546] and OS [median OS: 9.00 (95% CI: 5.31-12.70) months 9.40 (95% CI: 5.20-13.59) months, P=0.310]. ORR (21.1% 18.4%, P=0.773) and DCR (60.5% 60.5%, P=1.000) were of not statistically different between the IG and CG groups. As for safety, the IG group exhibited less frequent hypoproteinemia (31.6% 55.3%, P=0.037) and lactate dehydrogenase increased (18.4% 44.7%, P=0.014), while no differences in other adverse events were observed between the two groups.

CONCLUSIONS

Intermittent dose apatinib plus docetaxel was equally effective and more tolerable than continuous dose apatinib plus docetaxel as a second-line therapy in patients with advanced GC/GEJAC.

TRIAL REGISTRATION

ClinicalTrials.gov NCT03334591.

摘要

背景

既往关于晚期胃癌或胃食管交界腺癌（GC/GEJAC）二线治疗的研究报道，阿帕替尼联合化疗可改善治疗效果。然而，由于持续给药方案的耐受性，其获益有时受到限制。本随机对照研究旨在探讨间歇性或持续性给药阿帕替尼联合多西他赛作为晚期GC/GEJAC患者二线治疗的疗效和安全性。

方法

招募一线化疗失败的晚期GC/GEJAC患者（入组时间：2017年9月15日至2019年7月21日），采用区组随机化方法将其随机分为间歇给药组（IG组）或持续给药组（CG组）（1:1比例）。IG组患者接受阿帕替尼500 mg/d，连续服用5天，然后停药2天，联合多西他赛60 mg/m²，每3周1次，为期3周。CG组患者接受阿帕替尼500 mg/d联合多西他赛60 mg/m²，每3周1次，为期3周。每两个周期评估无进展生存期（PFS），每月进行随访。主要终点为PFS，次要终点为客观缓解率（ORR）、疾病控制率（DCR）、总生存期（OS）和安全性。

结果

共纳入76例符合条件患者并随机分组（1:1比例）。IG组与CG组的PFS相似[中位PFS：3.88（95%CI：1.72 - 6.03）个月对 3.98（95%CI：1.06 - 6.90）个月，P = 0.546]，OS也相似[中位OS：9.00（95%CI：5.31 - 12.70）个月对 9.40（95%CI：5.20 - 13.59）个月，P = 0.310]。IG组与CG组的ORR（21.1% 对 18.4%，P = 0.773）和DCR（60.5% 对 60.5%，P = 1.000）无统计学差异。在安全性方面，IG组低蛋白血症（31.6% 对 55.3%，P = 0.037）和乳酸脱氢酶升高（18.4% 对 44.7%，P = 0.014）的发生率较低，而两组其他不良事件无差异。