RESUMO
<p><b>BACKGROUND</b>Endostar™ (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.</p><p><b>METHODS</b>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/m² on 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/m² on 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 .</p><p><b>RESULTS</b>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 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (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 .</p><p><b>CONCLUSIONS</b>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 .</p>
RESUMO
<p><b>BACKGROUND</b>To evaluate and compare the effects and toxicity of the domestic product of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy and chemotherapy alone in the treatment of patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Two hundred patients with NSCLC in multicenter were randomly devided into trial group (150 cases) and control group (50 cases). Chemotherapy with CAP regimen was given to the patients. Meanwhile, rmhTNF injection of 4×10⁶U/m² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy cycle in the trial group. The control patients received chemotherapy alone. Twenty-one days were as a cycle, 2 cycles were given to each patient. The chemotherapeutic effects and toxicity were observed and compared between the two groups after the therapy.</p><p><b>RESULTS</b>of the 200 patients, 5 cases in the trial group and 3 cases in the control group were out of the trial because of economy. The other 192 cases (145 cases in the trial group and 47 cases in the control group) could be analyzed and evaluated the clinical effects and toxicity. The response rate of chemotherapy was 46.90% (68/145) in the trial group and 17.02% (8/47) in the control group respectively ( P =0.001). The KPS scores was 86.02±9.74 in the trial group, and 80.14±9.10 in the control group ( P =0.025). No significant difference of degree III+IV toxicity was observed between the two groups ( P > 0.05). The side effects related to rmhTNF included slight fever, cold-like symptoms, pain and red and swelling in the injection site. All of them were mild and didn't need any treatment and disappeared after the therapy. There were no severe abnormality of liver and kidney function and ECG in both groups.</p><p><b>CONCLUSIONS</b>The results demonstrate that the effects of domestic rmhTNF combined with chemotherapy are remarkably higher than that of chemotherapy alone in the treatment of NSCLC. rmhTNF can increase the sensitivity to chemotherapy and improve the quality of life of the patients with slight toxicity. Hence rmhTNF is worth expanding clinical use.</p>