Efficacy and safety of recombinant human endostatin combined with radiotherapy or chemoradiotherapy in patients with locally advanced non-small cell lung cancer: a pooled analysis.
Zhang Shu-Ling,Han Cheng-Bo,Sun Li,Huang Le-Tian,Ma Jie-Tao
Radiation oncology (London, England)
PURPOSE:To assess the efficacy and safety of recombinant human endostatin in combination with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). METHODS:We searched eligible literature in available databases using combinations of the following search terms: lung cancer, endostatin or endostar, radiotherapy or radiation therapy or chemoradiotherapy. The inclusion criteria were: prospective or retrospective (including single-arm) studies that evaluated the efficacy and safety of endostatin plus radiotherapy (ERT) or concurrent chemoradiotherapy (ECRT) in patients with LA-NSCLC. Primary outcomes included the following: objective response rate (ORR), local control rates (LCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Tests of heterogeneity, sensitivity, and publication bias were performed. RESULTS:A total of 271 patients with LA-NSCLC from 7 studies were enrolled, including six prospective trials and one retrospective study. The pooled median PFS was 11.3 months overall, 11.2 months in the ECRT group, and 11.8 months in the ERT group. Pooled median OS and ORR were 18.9 months and 77.2% overall, 18.4 months and 77.5% in the ECRT group, and 19.6 months and 76.1% in the ERT group, respectively. The incidences of major grade ≥ 3 AEs for all patients, subgroups of ECRT and ERT were 10.9% vs 11.9% vs 9.4% for radiation pneumonitis, 11.6% vs 12.2% vs 9.4% for radiation esophagitis, 35.5% vs 43.4% vs 0 for leukopenia, 27.8% vs 40.7% vs 2.1% for neutropenia, and 10.5% vs 12.3% vs 2.1% for anemia. CONCLUSIONS:Combined endostatin with RT or CCRT is effective and well tolerated in treating LA-NSCLC, and less toxicities occur. Further validation through prospective randomized control trials is required.
Different administration routes of recombinant human endostatin combined with concurrent chemoradiotherapy might lead to different efficacy and safety profile in unresectable stage III non-small cell lung cancer: Updated follow-up results from two phase II trials.
Honglian Ma,Zhouguang Hui,Fang Peng,Lujun Zhao,Dongming Li,Yujin Xu,Yong Bao,Liming Xu,Yirui Zhai,Xiao Hu,Jin Wang,Yue Kong,Lvhua Wang,Ming Chen
BACKGROUND:There are two main choices of administration route of recombinant human endostatin (Endostar) available and the treatment options of concurrent chemoradiotherapy (CCRT) have changed over time. The aim of this study was to observe the long-term efficacy and safety of different administration routes of Endostar combined with CCRT. METHODS:Patients with unresectable stage III non-small cell lung cancer (NSCLC) from two phase II trials were included as two cohorts. Both were treated with Endostar combined with CCRT. Endostar was administrated by intravenous injection (7.5 mg/m /day, seven days) in the IV arm and by continuous intravenous pumping (7.5 mg/m /24 hours, 120 hours) in the CIV arm. RESULTS:A total of 48 patients were included in the IV arm and 67 patients in the CIV arm. The median progression-free survival (PFS), overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) in the IV arm and CIV arm were 9.9 months versus 15.4 months (HR = 0.751, 95% CI 0.487-1.160, P = 0.200), 24.0 months versus 38.5 months (HR = 0.746, 95% CI 0.473-1.178, P = 0.209), 32.3 months versus 27.1 months (HR = 1.193, 95% CI 0.673-2.115, P = 0.546), 20.1 months versus 49.7 months (HR = 0.603, 95% CI 0.351-1.036, P = 0.067). The one, three, five-year PFS in the IV arm and CIV arm was 45.8% versus 52.9%, 18.3% versus 31.4%, and 18.3% versus 27.7% and the one, three, five-year OS was 81.2% versus 82.1%, 31.1% versus 50.3%, and 31.1% versus 41%, respectively. Incidence of hematological adverse reactions were numerically lower in the CIV arm than the IV arm. CONCLUSIONS:Endostar delivered by CIV with CCRT may be a better option than IV in terms of potential survival and safety for unresectable stage III NSCLC. KEY POINTS:Significant findings of the study Endostar delivered by continuous intravenous pumping might achieve more favorable survival over intravenous injection and reduce adverse hematological reactions in patients with unresectable stage III NSCLC treated with Endostar combined with CCRT.What this study adds The administration route of recombinant human endostatin is also one key factor for survival and safety to consider when treating patients with unresectable stage III NSCLC.
Current Status and Study Progress of Recombinant Human Endostatin in Cancer Treatment.
Li Kai,Shi Mingliang,Qin Shukui
Oncology and therapy
Angiogenesis plays fundamentally critical roles in solid-tumor pathogenesis, growth, invasion and metastasis. Endostatin, one of the most potent anti-angiogenic factors, was first isolated in Folkman's lab in 1997, and was reported to dramatically shrink tumor blood formation. But its insoluble and unstable nature coupled with the high cost of synthesizing the endostatin protein doomed it for clinical cancer treatment. Intrigued by Folkman's pioneering discoveries, Chinese scientists found a way to refold the protein, making it cost-effective to manufacture a recombinant human endostatin, a soluble and stable form of endostatin. A number of clinical studies have demonstrated the significant survival benefit of rh-endostatin in treating late stage non-small-cell lung carcinoma (NSCLC) and, as a result, rh-endostatin (Endostar) was approved by the State Food and Drug Administration of China (CFDA) in September of 2005 as a treatment option for NSCLC. Since then, increasing bodies of clinical data and experience have been obtained from a variety of other different cancers, such as small cell lung cancer, NSCLC in other settings, including malignant serous effusion, melanoma, colon cancer, gastric cancer, breast cancer, nasopharyngeal cancers, and others. This review aims at summarizing current clinical data of rh-endostatin including its survival benefits, optimized dosages, routes of administration, recommended duration and frequency of treatment, predictive biomarkers, and its safety profile in lung cancers as well as other cancers.
The role of VEGF in the diagnosis and treatment of malignant pleural effusion in patients with non‑small cell lung cancer (Review).
Chen Yao,Mathy Nicholas W,Lu Hongda
Molecular medicine reports
Malignant pleural effusion (MPE) is a severe medical condition, which can result in breathlessness, pain, cachexia and reduced physical activity. It can occur in almost all types of malignant tumors; however, lung cancer is the most common cause of MPE, accounting for ~1/3 of clinical cases. Although there are numerous therapeutic approaches currently available for the treatment of MPE, none are fully effective and the majority can only alleviate the symptoms of the patients. Vascular endothelial growth factor (VEGF) has now been recognized as one of the most important regulatory factors in tumor angiogenesis, which participates in the entire process of tumor growth through its function to stimulate tumor angiogenesis, activate host vascular endothelial cells and promote malignant proliferation. Novel drugs targeting VEGF, including endostar and bevacizumab, have been developed and approved for the treatment of various tumors. Data from recent clinical studies have demonstrated that drugs targeting VEGF are effective and safe for the clinical management of MPE. Therefore, VEGF‑targeting represents a promising novel strategy for the diagnosis and treatment of MPE. The present review summarized recent advances in the role of VEGF in the pathogenesis, diagnosis and clinical management of MPE in patients with non‑small cell lung cancer.
The effect of combining Endostar with radiotherapy on blood vessels, tumor-associated macrophages, and T cells in brain metastases of Lewis lung cancer.
Peng Ling,Wang Ying,Fei Shihong,Wei Chunhua,Tong Fan,Wu Gang,Ma Hong,Dong Xiaorong
Translational lung cancer research
Background:Combining Endostar (ES) with radiotherapy (RT) has shown a promising therapeutic effect on non-small cell lung carcinoma with brain metastases (BMs) in clinical practice. However, the specific mechanism is not yet fully understood. The present study aimed to investigate the effects of ES on blood vessels, tumor-associated macrophages (TAMs), and T cells in a tumor microenvironment treated with RT. Methods:BM models were established by stereotactic and intracarotid injection of luciferase-Lewis lung cancer (LLC) cells into female C57BL mice. The animals were randomly divided into 4 groups: normal saline (NS), ES, RT, and ES plus radiotherapy (ES + RT) groups. Tumor size was determined with the IVIS imaging system. Tumor specimens were stained with CD34 and α-SMA to investigate tumor vascular changes. The proportions of TAMs, CD4 T cells, and CD8 T cells in tumor tissues were determined by flow cytometry and immunofluorescence. The expressions of hypoxia-inducible factor 1α (HIF-1α) and CXCR4 were deduced using western blotting and immunohistochemistry (IHC). Results:ES + RT significantly suppressed tumor growth compared to the other 3 groups. RT decreased M1 and increased M2 in microglial cells and bone marrow-derived macrophages (BMDMs) relative to NS, while ES had the opposite effect. The ratio of CD8T/CD4T was increased in the ES + RT group compared to the other 3 groups. Tumor vascular maturity (α-SMA/CD34) was increased while HIF-1α was significantly suppressed in the ES + RT group. CXCR4 expression, which is involved in TAM recruitment, increased following RT, whereas, ES attenuated its expression. Conclusions:Our findings suggest that ES can promote the normalization of tumor blood vessels and increase the anti-tumor immune-related immune cells infiltrating the tumor following RT treatment.
Endostar combined with chemotherapy versus chemotherapy alone for advanced NSCLCs: a meta-analysis.
Ge Wei,Cao De-dong,Wang Hui-min,Jie Fang-fang,Zheng Yong-fa,Chen Yu
Asian Pacific journal of cancer prevention : APJCP
BACKGROUND:Use of recombinant human endostatin combined with conventional cytotoxic therapy to treat tumors has been growing because of evidence of increased efficacy. However, whether antiangiogenic therapy combined with chemotherapy really benefits patients with advanced non-small cell lung cancers (NSCLCs) remains unclear. OBJECTIVES:This study was conducted to evaluate the clinical efficacy and safety of rh-endostatin (Endostar) combined with chemotherapy in the treatment of NSCLC patients. METHODS:We selected data from the Cochrane Library, EMBASE, Medline, SCI,CBM, CNKI, to obtain all clinical controlled trials, including the addition of endostar to chemotherapy in advanced NSCLC patients. Fifteen trials with 1335 patients were included according to the inclusion criteria. All were randomized controlled trials, and two trials were adequate in reporting randomization. Seventeen trials did not mention the blinding methods. RESULTS:Meta-analysis indicated that the NPE arm (Vinorelbine+cisplatin+Endostar) had a different response rate compared with NP(Vinorelbine+cisplatin) arm (OR2.16, 95%CI 1.57 to 2.99). The incidences of severe leukopenia (OR0.94, 95%CI 0.66 to 1.32) and severe thrombocytopenia (OR 1.00, 95%CI 0.64 to 1.57) and nausea and vomiting (OR 0.85, 95%CI 0.61 to 1.20) were similar in the two arms. The NPE plus radiotherapy (RT) arm had a similar response rate compared with NP plus RT arm (OR 2.39, 95%CI 0.99 to 5.79), as were the incidences of leukopenia (OR0.83, 95%CI 0.35 to 1.94), thrombocytopenia (OR 0.78, 95%CI 0.19 to 3.16) and radiation esophagitis (OR 1.00, 95%CI 0.40 to 2.49). CONCLUSIONS:Our results suggested that in the treatment of advanced NSCLC, endostar in combination with platinum-based chemotherapy could improve the response rate without obviously increasing side effects.
Synergic effect of PD-1 blockade and endostar on the PI3K/AKT/mTOR-mediated autophagy and angiogenesis in Lewis lung carcinoma mouse model.
Wu Jing,Zhao Xiaogang,Sun Qifeng,Jiang Yunfeng,Zhang Weiquan,Luo Junwen,Li Yixin
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
BACKGROUND:Immunotherapy has been shown to be effective as a first-line treatment option for non-small cell lung cancer (NSCLC) patients. Unfortunately, it has failed to acquire an anticipant anti-tumour effect for relatively lower clinical benefit rates. It is therefore important to identify novel strategies for improving immunotherapy. Endostar is a novel recombinant human endostatin that exerts its anti-angiogenic effects via vascular endothelial growth factor (VEGF)-related signalling pathways. Anti-programmed death receptor 1 (PD-1) antibody is an immune checkpoint inhibitor that was developed to stimulate the immune system. In this study, the synergy of PD-1 blockade and endostar was assessed in a lung carcinoma mouse model. METHODS:Lewis lung carcinoma (LLC)-bearing mice were randomly assigned into three groups: controls, anti-PD-1 and anti-PD-1+endostar. The levels of cytokines such as interleukin (IL)-17, transforming growth factor-β1 (TGF-β1) and interferon-γ (IFN-γ) were measured with enzyme-linked immune sorbent assay (ELISA). The expression of VEGF, CD34 and CD31 was assessed with immunohistochemistry (IHC). The proportion of mature dendritic cells (mDC) and myeloid-derived suppressor cells (MDSC) was analysed with flow cytometry. The major proteins in PI3K/AKT/mTOR and autophagy were quantified with Western blot. RESULTS:Anti-PD-1 combined with endostar dramatically suppressed tumour growth in LLC mouse models. This synergistic effect resulted in decreased pro-inflammatory cytokine IL-17 and immunosuppressive factor TGF-β1 levels, increased IFN-γ secretion, reduced myeloid-derived suppressor cell (MDSC) accumulation, and reversed CD8 + T cell suppression. The expression of VEGF, CD34 and CD31 was significantly down-regulated, while tumour cell apoptosis and PI3K/AKT/mTOR-mediated autophagy was up-regulated. CONCLUSION:The combination of anti-PD-1 and endostar has a remarkably synergic effect on LLC tumour growth by means of improving the tumour microenvironment and activating autophagy.
Endostar improved efficacy of concurrent chemoradiotherapy with vinorelbine plus carboplatin in locally advanced lung squamous cell carcinoma patients with high serum Lp(a) concentration.
Xu Hailing,Lv Dongqing,Meng Yinnan,Wang Miao,Wang Wei,Zhou Chao,Zhou Suna,Chen Xiaofeng,Yang Haihua
Annals of palliative medicine
BACKGROUND:The role of vascular targeting therapy combined with concurrent chemoradiotherapy (CRT) has produced many inconsistent results in locally advanced non-small-cell lung cancer (NSCLC), especially in lung squamous cell carcinoma (LSCC). Lipoprotein (a) [Lp(a)] may be critical in the development of tumor angiogenesis, and its levels are individualized and determined genetically. This study aimed to determine whether Lp(a) is correlated with effects of recombinant human endostatin (Endostar) combined with concurrent CRT for locally advanced LSCC. METHODS:Patients with locally advanced LSCC from December 2008 to December 2017 were retrospectively analyzed. Patients were divided into two groups: (I) a chemoradiotherapy group (CRT group) which received weekly vinorelbine and carboplatin concurrently with radiotherapy 60Gy, and (II) an Endostar in combination with chemoradiotherapy group (ECRT group) which received Endostar intravenous drip for 1-14 days (every 3 weeks) concurrently with CRT. Fasting venous blood samples for serum Lp(a) in all patients were collected before the treatment. The effect of Endostar was assessed by stratified analysis. RESULTS:A total of 94 patients were recruited in this study. There were 59 cases in the CRT group and 35 cases in the ECRT group. Overall, the median progression-free survival (PFS) was 9.6 vs. 14.2 months (P=0.0671), and the overall survival (OS) was 15.0 vs. 20.6 months (P=0.114), in the CRT and ECRT groups respectively. The median of Lp(a) was 218 mg/L. In patients with serum Lp(a) less than 218 mg/L, the median PFS was 10.0 vs. 9.4 months (P=0.406), and the OS was 15.4 vs. 16.3 months (P=0.958) in the CRT and ECRT groups, respectively. However, in patients with serum Lp(a) higher than 218mg/L, the median PFS was 9.0 vs.15.8 months (P=0.011), and the OS was 14.0 vs. 21.1 months (P=0.055), in the CRT and ECRT groups, respectively. Cox proportional hazard model analysis revealed that a high concentration of Lp(a), ≥218 mg/L, is a prognostic factor for PFS [hazard rate (HR), 0.43 (0.23-0.81)] and OS [HR, 0.52 (0.27-0.98)] in locally advanced LSCC (P<0.05). CONCLUSIONS:The serum concentration of Lp(a) may serve as a biomarker to identify the patients who would benefit from Endostar treatment with concurrent CRT in stage III LSCC.
Efficacy and safety of rh-endostatin (Endostar) combined with pemetrexed/cisplatin followed by rh-endostatin plus pemetrexed maintenance in non-small cell lung cancer: A retrospective comparison with standard chemotherapy.
Zhou Shengyu,Zuo Lijie,He Xiaohui,Pi Jinping,Jin Jun,Shi Yuankai
BACKGROUND:Recombinant human endostatin (rh-endostatin) plus standard chemotherapy in advanced non-small cell lung cancer (NSCLC) patients has shown improved efficacy; however, it is unclear whether it is effective and safe when added to pemetrexed/cisplatin and used as maintenance therapy. METHODS:We retrospectively evaluated the data of untreated NSCLC patients administered rh-endostatin plus pemetrexed/cisplatin or pemetrexed/cisplatin. The primary endpoint was progression-free survival (PFS). RESULTS:Fifty-six and 39 patients received rh-endostatin plus pemetrexed/cisplatin and pemetrexed/cisplatin, and 34 and 29 underwent maintenance treatment, respectively. The median PFS was 10 months (95% confidence interval [CI] 5.85-14.15) in the rh-endostatin and 8.2 months (4.04-12.36) in the chemotherapy group, but the difference was not statistically significant (P = 0.13). In patients administered maintenance treatment, rh-endostatin plus pemetrexed was associated with prolonged PFS compared to single-agent pemetrexed when PFS was calculated from first dosing (13.7 [9.41-17.99] vs. 8.2 [4.16-12.24]; P = 0.032); however, PFS did not differ between the groups (hazard ratio 0.618; 95% CI 0.368-1.038; P = 0.069) after adjusting for clinical factors. No difference was observed in the objective response rate between the groups (48.2% vs. 38.5%; P = 0.346), with the exception of men (62.1% vs. 33.3%; P = 0.032) or in the incidence of drug-related or grade 3-4 adverse events. CONCLUSION:In previously untreated, advanced-stage NSCLC patients, first-line treatment with pemetrexed/cisplatin plus rh-endostatin did not prolong PFS or overall survival when compared to pemetrexed/cisplatin, but a trend of improved PFS was observed in patients administered maintenance rh-endostatin plus pemetrexed.
Enhanced antitumor and anti-angiogenic effects of metronomic Vinorelbine combined with Endostar on Lewis lung carcinoma.
Qin Rong-Sheng,Zhang Zhen-Hua,Zhu Neng-Ping,Chen Fei,Guo Qian,Hu Hao-Wen,Fu Shao-Zhi,Liu Shan-Shan,Chen Yue,Fan Juan,Han Yun-Wei
BACKGROUND:Conventional chemotherapy is commonly used to treat non-small cell lung cancer (NSCLC) however it increases therapeutic resistance. In contrast, metronomic chemotherapy (MET) is based on frequent drug administration at lower doses, resulting in inhibition of neovascularization and induction of tumor dormancy. This study aims to evaluate the inhibitory effects, adverse events, and potential mechanisms of MET Vinorelbine (NVB) combined with an angiogenesis inhibitor (Endostar). METHODS:Circulating endothelial progenitor cells (CEPs), apoptosis rate, expression of CD31, vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1α) were determined using flow cytometry, western blot analysis, immunofluorescence staining and Enzyme-linked immunosorbent assay (ELISA) analysis. And some animals were also observed using micro fluorine-18-deoxyglucose PET/computed tomography (F-FDG PET/CT) to identify changes by comparing SUVmax values. In addition, white blood cell (WBC) counts and H&E-stained sections of liver, lungs, kidney, and heart were performed in order to monitor toxicity assessments. RESULTS:We found that treatment with MET NVB + Endo was most effective in inhibiting tumor growth, decreasing expression of CD31, VEGF, HIF-1α, and CEPs, and reducing side effects, inducing apoptosis, such as expression of Bcl-2, Bax and caspase-3. Administration with a maximum tolerated dose of NVB combined with Endostar (MTD NVB + Endo) demonstrated similar anti-tumor effects, including changes in glucose metabolism with micro fluorine-18-deoxyglucose PET/computed tomography (F-FDG PET/CT) imaging, however angiogenesis was not inhibited. Compared with either agent alone, the combination of drugs resulted in better anti-tumor effects. CONCLUSION:These results indicated that MET NVB combined with Endo significantly enhanced anti-tumor and anti-angiogenic responses without overt toxicity in a xenograft model of human lung cancer.
Chemotherapy combined with Endostar as salvage treatment for EGFR-tyrosine kinase inhibitor primary resistance in an advanced non-small cell lung cancer patient with EGFR L858R mutation and ROS1 fusion: A case report.
Qiu Dong,Zhang Yu,Xue Ying-Bo,Shen Qi,Li Hang,Huang Ping,Hu Jian-Jun,Wang Yong-Sheng
EGFR-activating mutations have been recognized as the most important predictor of response to EGFR-tyrosine kinase inhibitors (TKIs); however, 20-30% of patients harboring EGFR-activating mutations show poor responses. The mechanisms of such EGFR-TKI primary resistance are still poorly understood. In our case, a non-small cell lung cancer patient developed intrinsic EGFR-TKI resistance and was then confirmed to simultaneously harbor an L858R mutation and ROS1 rearrangement. Salvage chemotherapy plus Endostar showed enduring therapeutic effects, achieving a disease-free survival period of 24 months and overall survival of 30 months. This suggests that co-activation of different oncogenic signal pathways might be a potential mechanism of EGFR-TKI primary resistance. Chemotherapy combined with anti-angiogenesis should be considered an important salvage strategy. Further studies are warranted to verify these findings and explore the underlying mechanisms involved.
Predictors for the efficacy of Endostar combined with neoadjuvant chemotherapy for stage IIIA (N2) NSCLC.
Zhao Xiaoliang,Wen Xiaohua,Wei Wei,Su Yanjun,You Jian,Gong Liqun,Zhang Zhenfa,Wang Meng,Xiao Jianyu,Wei Xiyin,Wang Changli
Cancer biomarkers : section A of Disease markers
BACKGROUND:Endostar (rh-endostatin) is a new recombinant human endostatin, which could inhibit cell proliferation, angiogenesis, and tumor growth. OBJECTIVE:To explore anti-angiogenesis short-term efficacy combined with neoadjuvant chemotherapy for stage IIIA (N2) non-small cell lung cancer (NSCLC), and identify the potential predictive factors. METHODS:We pathologically examined 26 patients diagnosed with stage IIIA (N2) NSCLC who received NP chemotherapy alone or combined with Endostar, respectively. RESULTS:Our results indicated that total clinical benefit rate (CBR) 87.5% and 64% (p= 0.76), respectively. The clinical benefit (CB) patients in the treatment group showed significant changes in endothelial progenitor cells (EPC), vascular endothelial growth factor (VEGF), blood flow (BF), permeability surface (PMS), and microvascular density (MVD) before and after treatment. Compared with CB patients in the control group, changes in EPC and MVD (only) before and after treatment were significant. The variation of EPC, PMS, and MVD before and after treatment in the treatment group showed positive correlation with tumor regression rate (TRR) and the variation of MVD, whereas those of EPC and PMS demonstrated positive correlations with variation of MVD before and after treatment. CONCLUSION:Our findings suggested that PMS and EPC may be used as a predictive factor for the short-term efficacy of the combined therapy in NSCLC.
[A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC)].
Han Bao-hui,Xiu Qing-yu,Wang Hui-min,Shen Jie,Gu Ai-qin,Luo Yi,Bai Chun-xue,Guo Shu-liang,Liu Wen-chao,Zhuang Zhi-xiang,Zhang Yang,Zhao Yi-zhuo,Jiang Li-yan,Shi Chun-lei,Jin Bo,Zhou Jian-ying,Jin Xian-qiao
Zhonghua zhong liu za zhi [Chinese journal of oncology]
OBJECTIVE:To analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS:This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death. RESULTS:The objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05). CONCLUSIONS:Compared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.
Comparison of Endostar continuous versus intermittent intravenous infusion in combination with first-line chemotherapy in patients with advanced non-small cell lung cancer.
Cheng Yuan,Nie Ligong,Liu Ying,Jin Zhe,Wang Xi,Hu Zhanwei
BACKGROUND:Intravenous infusion of Endostar for three to four hours per day for 14 days reduces patient compliance and affects quality of life. Continuous intravenous infusion (CI) represents a novel method of administration; however, it is unclear whether it is effective and safe when compared to the traditional method. METHODS:We retrospectively reviewed patients with advanced non-small cell lung cancer (NSCLC) administered CI (20 patients) or intermittent intravenous infusion (II, 49 patients) of Endostar combined with first-line chemotherapy. Three patients in the II group discontinued therapy because of adverse effects. RESULTS:Median progression-free survival was 6.0 months in the CI group and 3.8 months in the II group, with no significant difference (P = 0.1). The objective response and disease control rates were also similar in the CI and II groups (40.0 vs. 32.6%, P = 0.562; 65 vs. 69.6%, P = 0.714, respectively). CONCLUSION:CI of Endostar combined with first-line chemotherapy for advanced NSCLC had similar progression-free survival, objective response, and overall response rates as II, with tolerable adverse effects.