2011世界肺癌大会(wclc)4篇恩度论文post

2011 世界肺癌大会（WCLC）4 篇恩度论文 POST 1、Recombinant human endostatin normalizes tumor vasculature and alleviates hypoxia in Lewis lung carcinomas M. Chen, F. Peng, Z.M. Xu, J. Wang, Y. Bao, Y.Y. Chen, X. Hu, Y. Wang, Q.C. Zhou, H.L. Ma Sun Yat-Sen University Cancer Center/CHINA 重组人血管内皮抑素（恩度）对 Lewis 肺癌的肿瘤血管正常化及改善乏氧作用，中山肿瘤医院陈明教授 Background: Tumor vessels are structurally and functionally abnormal with defective endothelium, pericyte coverage, and basement membrane. Most antiangiogenic cancer therapies focus on the destruction of solid tumors by eradication of their supporting vasculature. However, antiangiogenic therapy may “normalize” the tumor vasculature for a short period of time, thereby providing a window of opportunity for enhanced sensitivity to radiation treatment.We investigated whether recombinant human endostatin created a “vascular normalization window” within tumors prior to vascular pruning to alleviate hypoxia in Lewis lung carcinomas in mice. Methods: (1)Kinetic changes in morphology of tumor vasculature in response to treatment with recombinant human endostatin were detected under a confocal microscope with immunofluorescent staining in Lewis lung carcinomas in mice.(2)The time course of hypoxic tumor fraction was assessed with immunohistochemical staining.(3)Effects on tumor growth were monitored as indicated in the growth curve of tumors. Results: Vascularity of the tumors was reduced over time by recombinant human endostatin treatment and significantly regressed for 9 days relative to the control group (Fig 1a-b). During recombinant human endostatin treatment, pericyte coverage increased by day3, increased markedly by day 5, and fell again by day 7 (Fig 1c-f). The vascular basement membrane (BM) was thin and closely associated with endothelial cells after recombinant human endostatin treatment, but appeared thickened, loosely associated with endothelial cells in control tumors (Fig 1g-n). The decrease in hypoxic tumor fraction on the 5th day after treatment was also found (Fig 2a). Tumor growth was not accelerated 5 days after recombinant human endostatin treatment (Fig 2b). Conclusion: Recombinant human endostatin can normalize tumor vasculature within day 3 to 7, leading to improved tumor oxygenation. The results provide important experimental basis for combining recombinant human endostatin with radiation therapy in human tumors. 2、Circulating endothelial progenitor cells in resectable non-small cell lung cancer during adjuvant chemotherapy combined with endostar Y. Yu, Z. Song, S. Lu Shanghai Chest Hospital, Jiaotong University, Shanghai/CHINA 对于 NSCLC 术后辅助化疗联合恩度治疗中内皮祖细胞的研究，上海胸科医院 陆舜教授 Background: Antiangiogenic molecules can inhibit neovascularization in lung cancer, but their effect on circulating endothelial progenitor cells(cEPCs) is still unclear. Several hypotheses have been proposed that antiangiogenic drugs enhance the treatment efficacy of cytotoxic chemotherapy, including impairing the ability of tumors to regrow after therapy. Therefore, our study aims to examine the level of cEPCs (VEGFR2+ /CD133+) in the peripheral blood of resectable non-small cell lung cancer patients(NSCLC) treated by either chemotherapy combined with endostar(recombinant human endostatin) or chemotherapy alone as adjuvant therapy. Methods: Thirty three patients with resectable NSCLC were enrolled. Ten healthy individuals were as control. The blood samples of the patients were from a clinical trial(NCT01124253). Among them,18 patients treated by chemotherapy alone and 15 patients treated by chemotherapy combined with endostar. Peripheral blood was taken from the patients before surgery and after postoperative adjuvant therapy. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll density gradient centrifugation. cEPCs labeled with VEGFR2, CD133 were counted by flow cytometry. Furthermore, we measured VEGFR2, CD133, CD34, and VE-cadherin mRNA in blood samples by means of a quantitative reverse transcription-PCR approach. Results: The percentage of cEPCs in the total PBMCs was 0.26%±0.14% in NSCLC patients without treatment intervention versus 0.045±0.032% in healthy controls( p = 0.00). There was a significant difference of cEPCs numbers in stage III compared with III ( p = 0.027) in the preoperative blood samples. The cEPCs numbers were significant lower in the combination therapy group than in chemotherapy alone group in the postoperative blood samples (p=0.014). Time to disease progression(TTP) in the patients with low cEPCs number (less than 0.35%) was longer than in those with high cEPCs number after adjuvant treatment (p =0.00, log rank). The preoperative VEGFR2 mRNA level was significantly correlated to disease progression ( p = 0.00, log rank test). Conclusion: This study showed that NSCLC patients had high cEPCs numbers. An early antiangiogenic therapy in combination with chemotherapy may be beneficial for the success of resectable NSCLC adjuvant therapy, and cEPCs may be a novel biomarker in those patients with no measurable targets. 3、An Update of the Phase III Study of Adjuvant Vinorelbine Plus Cisplatin (NP) Versus NP Plus Endostar (NPE) in Patients with Completely Resected Stage IB-IIIA Non-Small Cell Lung Cancer (NSCLC) J. He1, X. Zhang1, J. Li1, B. Han2, Y. Liu3, S. Wu4, Y. Kuang5, Y. Shen6, C. Chen7, Q. Wang8, Q. Li9, H. Ma10, S. Xu11, S. Xu12, P. Wang13, W. Mao14, Z. Pang5, S. Hou15, Y. Yang16 1Cancer Institute and Hospital, Chinese Academy of Medical Sciences/CHINA, 2Shanghai Jiaotong University Affiliated Shanghai Chest Hospital/CHINA, 3Liaoning Cancer Hospital arm B: 456) from 43 centers in China were enrolled between 9/2007 and 12/2010. Two arms were well-balanced with regard to age, gender, histology, stage, and resection type. 80 patients in arm A and 91 patients in arm B had relapsed disease. The median RFS was 27.7 months in arm A and 24.6 months in arm B (p=0.6009). 80.3% of patients in arm A finished 4 cycles of treatment and 77.8% of patients in arm B received 4 cycles of chemotherapy. Median survival time was not available at this moment because only very few patients had died. Grade 3/4 toxicities in arm A included leukopenia (58.4%), neutropenia (77.4%), anemia (13.1%), nausea (12.4%). Grade 3/4 toxicities in arm B included leukopenia (35.5%) neutropenia (61.6%), anemia (8.5%) and nausea (8.5%). It is worth noting that the incidence of cardiac toxicities in arm A (28.0%) was higher than that in arm B (21.1%). Conclusion: The preliminary result showed that patients in arm A experienced a longer median relapse-free survival time than in arm B (27.7 months vs. 24.6 months), although the difference was not statistically significant until now. The toxicity profiles for both arms were tolerable in this study. The patient follow- up is ongoing. 4、A prospective phase I/II study of recombinant endostatin (endostar) combined with concurrent chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer: a preliminary report M. Chen1, Y. Bao1, Q.C. Zhou1, X. Hu1, Z.H. Yu2, Y.C. Cai3, J.C. Li4, Z.B. Cheng5, L. Chen6, Y. Wang1, J. Wang1, F. Peng1, Z.M. Xu1, H.L. Ma1, R.B. Lu1, H.Q. Dai1 1Sun Yat-Sen University Cancer Center/CHINA, 2Affiliated Hospital Of Guangdong Medical College/CHINA, 3First People Hospital of Zhaoqing/CHINA, 4Fujian Provincial Tumor Hospital/CHINA, 5The Fifth/CHINA, 6Affiliated Hospital of Guangxi Medical College/CHINA 不可切除的 III 期 NSCLC 同步放化疗联合重组人血管内抑制素的前瞻性临床研究，中山肿瘤医院陈明教授 Background: More than 3000 patients with advanced non-small cell lung cancer (NSCLC) have been treated with recombinant endostatin (endostar) combined with chemotherapy in China. Recently our experimental study showed a synergistic effect between endostar and irradiation in xenografts of Lewis lung in mice. The critical mechanism of which is tumor vasculature normalization occurred in a certain duration. We designed this study to evaluate safety and efficacy of endostar combined with standard current chemoradiation therapy (CCRT) in patients with unresectable stage III NSCLC. Methods: Patients were administered with endostatin 7.5mg/m2 (week0, 2, 4, 6), docetaxel 65mg/m2 (Day 1, 29) and cisplatin 65mg/m2 (Day1, 29). Radiotherapy consists of 2.0 Gy in 30-33 fractions over 6-7 weeks to a total dose of 60-66 Gy. Tumor response was evaluated with thoracic CT scans performed 4 weeks after completion of treatment in accordance with RECIST criteria. Acute toxicities was evaluated with NCI-CTC AE version 3.0 Results: From March 2009 to December 2010, 37 patients completed treatment and were available for evaluation. Thirty-three patients remain alive. The median follow-up time was 9.5 months (1-22 months). Six (16.2%) patients achieved complete response (CR), 21 (56.8%) partial response (PR), 6 (16.2%) stable disease (SD), and 4 (10.8%) progressive disease (PD). Endostar did not increase toxicity to CCRT. Hematological and non-hematological toxicities were acceptable. No patient developed cardiovascular toxicity. Table 1. Acute Hematological toxicity Toxicity Grade 1 Grade 2 Grade 3 Grade 4 Leucopenia 15(40.5%) 5(13.5%) 5(13.5%) 11(29.7%) Neutropenia 4(10.8%) 3(8.1%) 4(10.8%) 10(27.0%) Lymphocytopenia 2(5.4%) 3(8.1%) 19(51.4%) 12(32.4%) Anemia 18(48.6%) 5(13.5%) 1(2.7%) 0 Thrombocytopenia 3(8.1%) 4(10.8%) 2(5.4%) 0 Table 2. Acute Non-hematological toxicity Toxicity Grade 1 Grade 2 Grade 3 Grade 4 Esophagitis 2(5.4%) 31(83.8%) 4(10.8%) 0 Dermatitis 34(91.9%) 1(2.7%) 2(5.4%) 0 Alopecia 30(81.1%) 7(18.9%) 0 0 Pneumonitis 5(13.5%) 4(10.8%) 6(16.2%) 0 Anorexia 19(51.4%) 16(43.2%) 2(5.4%) 0 Nausea 18(48.6%) 6(16.2%) 0 0 Vomiting 7(18.9%) 3(8.1%) 2(5.4%) 0 Peripheral neuritis 2(5.4%) 0 0 0 Allergy 0 1(2.7%) 0 0 Fatigue 11(29.7%) 6(16.2%) 0 0 Cough 16(43.2%) 5(13.5%) 7(18.9%) 0 cardiovascular 0 0 0 0 Conclusion: The preliminary results showed that endostar combined with CCRT for unresectable stage III NSCLC was safe and the short term outcomes were promising. Further investigation is warranted.