A randomized, double-blind, placebo-controlled study of B-cell lymphoma 2 homology 3 mimetic gossypol combined with docetaxel and cisplatin for advanced non-small cell lung cancer with high expression of apurinic/apyrimidinic endonuclease 1
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Published:2020-06-11
Issue:6
Volume:38
Page:1862-1871
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ISSN:0167-6997
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Container-title:Investigational New Drugs
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language:en
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Short-container-title:Invest New Drugs
Author:
Wang Yuxiao,Li Xuemei,Zhang Liang,Li Mengxia,Dai Nan,Luo Hao,Shan Jinlu,Yang Xueqin,Xu Mingfang,Feng Yan,Xu Chengxiong,Qian Chengyuan,Wang Dong
Abstract
SummaryBackground Overexpression of apurinic/apyrimidinic endonuclease 1 (APE1) is an important cause of poor chemotherapeutic efficacy in advanced non-small cell lung cancer (NSCLC) patients. Gossypol, a new inhibitor of APE1, in combination with docetaxel and cisplatin is believed to improve the efficacy of chemotherapy for advanced NSCLC with high APE1 expression. Methods Sixty-two patients were randomly assigned to two groups. Thirty-one patients in the experimental group received 75 mg/m2 docetaxel and 75 mg/m2 cisplatin on day 1 with gossypol administered at 20 mg once daily on days 1 to 14 every 21 days. The control group received placebo with the same docetaxel and cisplatin regimen. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and toxicity. Results There were no significant differences in PFS and OS between the experimental group and the control group. The median PFS (mPFS) in the experimental and control groups was 7.43 and 4.9 months, respectively (HR = 0.54; p = 0.06), and the median OS (mOS) was 18.37 and 14.7 months, respectively (HR = 0.68; p = 0.27). No significant differences in response rate and serious adverse events were found between the groups. Conclusion The experimental group had a better mPFS and mOS than did the control group, though no significant difference was observed. Because the regimen of gossypol combined with docetaxel and cisplatin was well tolerated, future studies with larger sample sizes should be performed.
Funder
National Natural Science Foundation of China Army Medical University Chongqing Science and Technology Commission
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Pharmacology,Oncology
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