一项关于羧甲氨基三唑联合化疗治疗晚期非小细胞肺癌的III期随机双盲对照试验。
A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer.
作者信息
Si Xiaoyan, Wang Jinwan, Cheng Ying, Shi Jianhua, Cui Liying, Zhang Helong, Huang Yunchao, Liu Wei, Chen Lei, Zhu Jiang, Zhang Shucai, Li Wei, Sun Yan, Wang Hanping, Zhang Xiaotong, Wang Mengzhao, Yang Lin, Zhang Li
机构信息
Division of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.
Department of Medical Oncology, Chinese Academy of Medical Sciences Cancer Institute and Hospital, Beijing, China.
出版信息
Ther Adv Med Oncol. 2020 Nov 24;12:1758835920965849. doi: 10.1177/1758835920965849. eCollection 2020.
BACKGROUND
Carboxyamidotriazole (CAI), a calcium channel blocker, inhibits tumor cell proliferation, metastasis, and angiogenesis. This trial aimed to determine whether CAI combined with conventional chemotherapy could prolong progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients.
METHODS
Patients were assigned into groups (3:1 ratio) to receive either chemotherapy + CAI or chemotherapy alone. Cisplatin (25 mg/m) was administered by intravenous infusion on days 1, 2, and 3, and vinorelbine (25 mg/m) on days 1 and 8 of each 3-week cycle for four cycles. CAI was administered at 100 mg daily with concomitant chemotherapy; this treatment was continued after chemotherapy was ceased until serious toxicity or disease progression had occurred. PFS was the primary endpoint, and the secondary endpoints were objective response rate (ORR), disease control rate, overall survival (OS), and quality of life.
RESULTS
In total, 495 patients were enrolled in the trial: 378 in the chemotherapy + CAI group and 117 in the chemotherapy + placebo group. PFS was significantly greater in the chemotherapy + CAI [median, 134 days; 95% confidence interval (CI) 127-139] than in the chemotherapy + placebo (median, 98 days; 95% CI: 88-125) group, with a hazard ratio of 0.690 (95% CI: 0.539-0.883; = 0.003). There was no difference in the OS rates of both groups. The ORR was greater in the chemotherapy + CAI group than in the chemotherapy + placebo group (34.6% 25.0%, = 0.042). Adverse events of ⩾grade 3 occurred more frequently in the CAI group [256 (68.1%) 64 (55.2%); = 0.014].
CONCLUSION
CAI + platinum-based chemotherapy prolonged PFS and could be a useful therapeutic option to treat NSCLC.
CLINICAL TRIAL REGISTRATION
chinadrugtrials.org.cn identifier: CTR20160395.
背景
羧甲氨基三唑（CAI）是一种钙通道阻滞剂，可抑制肿瘤细胞增殖、转移和血管生成。本试验旨在确定CAI联合传统化疗能否延长非小细胞肺癌（NSCLC）患者的无进展生存期（PFS）。
方法
患者按3:1的比例分组，分别接受化疗+CAI或单纯化疗。在每3周一个周期的第1、2和3天静脉输注顺铂（25mg/m²），第1天和第8天静脉输注长春瑞滨（25mg/m²），共进行4个周期。CAI在化疗期间每日给药100mg；化疗结束后继续给药，直至出现严重毒性或疾病进展。PFS是主要终点，次要终点包括客观缓解率（ORR）、疾病控制率、总生存期（OS）和生活质量。
结果
共有495例患者入组本试验：化疗+CAI组378例，化疗+安慰剂组117例。化疗+CAI组的PFS显著长于化疗+安慰剂组[中位数为134天；95%置信区间（CI）为127-139]，化疗+安慰剂组的PFS中位数为98天；95%CI：88-125），风险比为0.690（95%CI：0.539-0.883；P=0.003）。两组的OS率无差异。化疗+CAI组的ORR高于化疗+安慰剂组（34.6%对25.0%，P=0.042）。≥3级不良事件在CAI组中更频繁发生[256例（68.1%）对64例（55.2%）；P=0.014]。
结论
CAI+铂类化疗可延长PFS，可能是治疗NSCLC的一种有效治疗选择。
临床试验注册
中国药物临床试验登记网标识符：CTR20160395。
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