Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients

Background and objective Endostar TM （rh-endostatin, YH-16） is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase Ⅰ and phase Ⅱ studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression （TTP） ,clinical benefit andsafety in patients with advanced non-small cell lung cancer （ NSCLC） , who were treated with YH-16 plus vi-norelbine and cisplatin （NP） or placebo plus NP.Methods Four hundred and ninety-three histologically or cy-tologically confirmed stage ⅢB and Ⅳ NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0--2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 （vinorelbine 25 mg/ m2on day 1 and day 5 ,cisplatin 30mg/m2 on days 2 to 4 , YH-167.5mg/m2 on days 1 to 14） or control group : NP plus placebo （vinorelbine 25 mg/m2 on day 1 and day 5 ,cis-platin 30 mg/ m2on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14） every 3 weeks for 2--6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .Results Of 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup （P=0 .0003） . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively （P 0 .05） . The score of quality oflife in trial group was significantly higher than that in control group （P=0 .0155） after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .Conclusion The addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients . DOI: 10.3779/j.issn.1009-3419.2005.04.07