A multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of paclitaxel-carboplatin alone or with endostar for advanced non-small cell lung cancer.
ABSTRACT Recombinant human endostatin is a novel inhibitor of tumor angiogenesis that acts specifically on neovascular endothelial cells. Studies have shown that endostar plus vinorelbine-cisplatin chemotherapy could improve objective response rates (ORR) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients. This study is to explore the clinical efficacy of endostar plus paclitaxel-carboplatin (TC) in advanced NSCLC patients.
A phase II, multicenter, randomized, double-blind, placebo-controlled study was carried out. Patients were randomly assigned to the treatment (TC + endostar) or the control group (TC + placebo). The efficacy was evaluated at the end of each cycle. Follow-up continued until disease progression or death.
A total of 126 patients were enrolled, of whom 122 were evaluable, with 61 in each group. ORR was 39.3% in the treatment group versus 23.0% in the control group (p = 0.078), and the disease control rate was 90.2% versus 67.2% (p = 0.004), respectively. The median progression-free survival (PFS) was 7.1 versus 6.3 months (p = 0.522) in the treatment and control groups, the 24-week rate of PFS was 78% versus 59% (p = 0.017), and the median OS was 17.6 versus 15.8 months (p = 0.696), respectively. There were no significant differences, either in the incidence of adverse events or serious adverse events, between the two groups.
In previously untreated, advanced NSCLC patients, treatment with TC plus endostar seemed to improve ORR. However, the differences in PFS or OS between the two groups were not statistically significant. Treatment with TC plus endostar exhibited a good safety profile.
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ABSTRACT: The aim of this study was to evaluate the safety of the continuous administration of recombinant human endostatin (Endostar) in healthy mice. A total of 16 nude mice were randomly divided into four treatment groups: a continuous administration group injected intraperitoneally (i.p.) with 14 mg/kg Endostar over seven days, an intermittent administration group injected i.p. with 2 mg/kg Endostar daily for seven days, a saline injection group and an untreated control group. All mice were implanted with an intraperitoneal mini-osmotic drug pump filled with Endostar or saline. The serum concentration of Endostar, the cell fraction of CD11b(-)CD146(+)CD105(+) vascular endothelial cells in the peripheral blood, the injury of the myocardial, lung and kidney tissues and the density of microvessels within these organs were observed 24 h after the termination of drug or saline administration. Only trace amounts of Endostar were detected in the serum of the continuous administration and intermittent administration groups. Myocardial, lung and kidney tissues exhibited no detectable signs of injury and no differences in the density of microvessels were found in these organs among the four groups. Yet, the cell fraction (in %) of CD11b(-)CD146(+)CD105(+) vascular endothelial cells in the peripheral blood was higher in the continuous administration group compared with that in the other treatment groups (P=0.011). This suggests that intermittent Endostar delivery did not significantly impact the vascular endothelium, while continuous Endostar administration may promote injury of the endothelium. In conclusion, the continuous administration of Endostar does not appear to be a safe method by which to administer this antiangiogenic agent to healthy nude mice.Experimental and therapeutic medicine 06/2012; 3(6):1018-1022. · 0.34 Impact Factor
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ABSTRACT: BACKGROUND: Many studies have investigated the efficacy of Endostar combined with platinum-based doublet chemotherapy (PBDC) versus PBDC alone for treating advanced non-small cell lung cancer (NSCLC). This study is a meta-analysis of available evidence. METHODS: Fifteen studies reporting Endostar combined with PBDC versus PBDC alone for treating advanced NSCLC were reviewed. Pooled odds ratios and hazard ratio with 95% confidence intervals were calculated using either the fixed effects model or random effects model. RESULTS: The overall response rate (ORR) and disease control rate (DCR) of Endostar combined with PBDC for treating NSCLC were significantly higher than those of PBDC alone, with 14.7% and 13.5% improvement, respectively (P < 0.00001). In addition, the time to progression (TTP) and quality of life (QOL) were improved after the treatment of Endostar combined with PBDC (P < 0.00001). The main adverse effects found in this review were hematological reactions, hepatic toxicity, and nausea/vomiting. Endostar combined with PBDC had a similar incidence of adverse reactions compared with PBDC alone (P < 0.05). CONCLUSIONS: Endostar combined with PBDC was associated with higher RR, DCR, and TTP as well as superior QOL profiles compared with PBDC alone. Endostar combined with PBDC had a similar incidence of adverse reactions compared with PBDC alone.World Journal of Surgical Oncology 08/2012; 10(1):170. · 1.09 Impact Factor
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ABSTRACT: BACKGROUND: Recombinant human endostatin (rh-endostatin) is a novel antiangiogenesis drug developed in China. Previous experiments have shown that rh-endostatin can inhibit the proliferation and migration of endothelial cells and some types of tumor cells. In this study, we evaluated the efficacy and safety profiles of combination therapy of rh-endostatin and neoadjuvant chemotherapy for breast cancer patients in a prospective, randomized, controlled, phase II trial. METHODS: Sixty-eight patients with core-biopsy confirmed breast cancer were allocated randomly to two groups to receive 3 cycles of intravenous administration of either neoadjuvant DE (docetaxel: 75 mg/m2, d1, epirubicin: 75 mg/m2, d1, every 3 weeks), or neoadjuvant DE combined with rh-endostatin (7.5 mg/m2, d1-d14, every 3 weeks). The primary end point was clinical response based upon Response Evaluation Criteria in Solid Tumors, and the secondary end point was safety and quality of life. RESULTS: All patients were assessable for toxicity and 64 (94.2%) were assessable for efficacy evaluation. The objective response rate was 67.7% for chemotherapy (n = 31) and 90.9% for rh-endostatin plus chemotherapy (n = 33) (P = 0.021). A retrospective subset analysis revealed that rh-endostatin was more effective in premenopausal patients and patients with ECOG score of zero (P = 0.002 and P = 0.049, respectively). Five patients in the rh-endostatin plus chemotherapy arm achieved pathologic complete response compared with 2 in the chemotherapy arm (P = 0.428). No significant difference was identified in quality of life score and side effects (P > 0.05). CONCLUSION: The combination of rh-endostatin with chemotherapy produced a higher tumor response rate without increasing toxicity in breast cancer patients.ClinicalTrials.gov Identifier: NCT00604435.BMC Cancer 05/2013; 13(1):248. · 3.33 Impact Factor