A Randomized, Double-blind, Placebo-controlled Study Of Gossypol Combined With Docetaxel And Cisplatin For Advanced Non-small Cell Lung Cancer With High Expression Of APE1

Background:Most non-small cell lung cancer(NSCLC)patients are diagnosed with advanced-stage disease,and lose the opportunity of surgical resection and choose chemotherapy.As the main treatment of advanced NSCLC,chemotherapy has not been improved in efficacy for a long time.Platinum-based chemotherapy is the first-line regimen of NSCLC chemotherapy,so platinum resistance may be the key to limit the efficacy.The overexpression of apurine/apyrimidine endonuclease 1(APE1)is an important reason for platinum resistance in advanced NSCLC.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/m~2 docetaxel and 75 mg/m~2 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),disease control rate(DCR),objective response rate(ORR)and toxicity.Results:There were no significant differences in PFS and OS between the experimental group and the control group.The median PFS(m PFS)in the experimental and control groups was 7.43 and 4.9 months,respectively(HR=0.54;p=0.06),and the median OS(m OS)was18.37 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:Although no statistically significant difference in PFS between the experimental group and the control group,the m PFS of the experimental group has a significant trend of prolongation than that of the control group.The regimen of gossypol combined with docetaxel and cisplatin is well tolerated,and a larger sample size will be studied in the future.