A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer

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) pa...

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Main Authors: Xiaoyan Si, Jinwan Wang, Ying Cheng, Jianhua Shi, Liying Cui, Helong Zhang, Yunchao Huang, Wei Liu, Lei Chen, Jiang Zhu, Shucai Zhang, Wei Li, Yan Sun, Hanping Wang, Xiaotong Zhang, Mengzhao Wang, Lin Yang, Li Zhang
Format: Article
Language:English
Published: SAGE Publishing 2020-11-01
Series:Therapeutic Advances in Medical Oncology
Online Access:https://doi.org/10.1177/1758835920965849
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spelling doaj-139061d82c9d427297f29127b1efa5a02020-12-01T08:05:11ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592020-11-011210.1177/1758835920965849A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancerXiaoyan SiJinwan WangYing ChengJianhua ShiLiying CuiHelong ZhangYunchao HuangWei LiuLei ChenJiang ZhuShucai ZhangWei LiYan SunHanping WangXiaotong ZhangMengzhao WangLin YangLi ZhangBackground: 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 2 ) was administered by intravenous infusion on days 1, 2, and 3, and vinorelbine (25 mg/m 2 ) 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; p  = 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% versus 25.0%, p  = 0.042). Adverse events of ⩾grade 3 occurred more frequently in the CAI group [256 (68.1%) versus 64 (55.2%); p  = 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: CTR20160395https://doi.org/10.1177/1758835920965849
collection DOAJ
language English
format Article
sources DOAJ
author Xiaoyan Si
Jinwan Wang
Ying Cheng
Jianhua Shi
Liying Cui
Helong Zhang
Yunchao Huang
Wei Liu
Lei Chen
Jiang Zhu
Shucai Zhang
Wei Li
Yan Sun
Hanping Wang
Xiaotong Zhang
Mengzhao Wang
Lin Yang
Li Zhang
spellingShingle Xiaoyan Si
Jinwan Wang
Ying Cheng
Jianhua Shi
Liying Cui
Helong Zhang
Yunchao Huang
Wei Liu
Lei Chen
Jiang Zhu
Shucai Zhang
Wei Li
Yan Sun
Hanping Wang
Xiaotong Zhang
Mengzhao Wang
Lin Yang
Li Zhang
A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer
Therapeutic Advances in Medical Oncology
author_facet Xiaoyan Si
Jinwan Wang
Ying Cheng
Jianhua Shi
Liying Cui
Helong Zhang
Yunchao Huang
Wei Liu
Lei Chen
Jiang Zhu
Shucai Zhang
Wei Li
Yan Sun
Hanping Wang
Xiaotong Zhang
Mengzhao Wang
Lin Yang
Li Zhang
author_sort Xiaoyan Si
title A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer
title_short A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer
title_full A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer
title_fullStr A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer
title_full_unstemmed A phase III, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer
title_sort phase iii, randomized, double-blind, controlled trial of carboxyamidotriazole plus chemotherapy for the treatment of advanced non-small cell lung cancer
publisher SAGE Publishing
series Therapeutic Advances in Medical Oncology
issn 1758-8359
publishDate 2020-11-01
description 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 2 ) was administered by intravenous infusion on days 1, 2, and 3, and vinorelbine (25 mg/m 2 ) 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; p  = 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% versus 25.0%, p  = 0.042). Adverse events of ⩾grade 3 occurred more frequently in the CAI group [256 (68.1%) versus 64 (55.2%); p  = 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
url https://doi.org/10.1177/1758835920965849
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