首页> 外文期刊>Cancer biology & therapy >Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab and has strong antitumor activity in advanced non-small-cell-lung cancer patients.
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Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab and has strong antitumor activity in advanced non-small-cell-lung cancer patients.

机译:分次顺铂和口服每日依托泊苷的剂量/密集节律化疗可增强贝伐单抗的抗血管生成作用,并在晚期非小细胞肺癌患者中具有强大的抗肿瘤活性。

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BACKGROUND: We designed a translational clinical trial to investigate whether a dose/dense chemotherapy regimen is able to enhance in patients with non-small-cell-lung-cancer (NSCLC) the anti-angiogenic effects of bevacizumab, a murine/human monoclonal antibody to the vasculo-endothelial-growth-factor (VEGF). We also evaluated the antitumor activity of this combination. RESULTS: The combined treatment induced a significant decline in the blood-perfusion of primary tumor (NMR-study); in serum levels of VEGF, angiopoietin-1, thrombospondin-1; and in the number of VEGF-transporting cells. In the group of 40 patients who received bevacizumab an objective response and a disease stabilization rate of 77.5% (95% CI, 75.63-93.17) and 15%, respectively, were recorded with a time to progression of 7.6 mo. Grade I-II hematological toxicity was the most common adverse event. Four early deaths within 3 mo, three cases of pneumonia, and six cases of mood depression at higher bevacizumab dosage were observed. The most active biological and maximum tolerated dose were 5 and 7.5 mg/kg, respectively. PATIENTS AND METHODS: Forty-eight patients (42 males and six females) with stage III B/IV NSCLC, a mean age of 68 y, and ECOG
机译:背景:我们设计了一项转化临床试验,以研究剂量/密集化疗方案是否能够增强非小细胞肺癌(NSCLC)患者的鼠/人单克隆抗体贝伐单抗的抗血管生成作用血管内皮生长因子(VEGF)。我们还评估了这种组合的抗肿瘤活性。结果:联合治疗引起原发性肿瘤的血液灌注显着下降(核磁共振研究)。血清中VEGF,血管生成素-1,血小板反应蛋白1的水平;以及VEGF转运细胞的数量在接受贝伐单抗治疗的40名患者中,客观反应和疾病稳定率分别为7.6 mo(进展时间)为77.5%(95%CI,75.63-93.17)和15%。 I-II级血液学毒性是最常见的不良事件。在较高贝伐单抗剂量下,观察到3个月内4例早期死亡,3例肺炎和6例情绪低落。最活跃的生物学剂量和最大耐受剂量分别为5和7.5 mg / kg。患者与方法:该研究纳入了38例III B / IV期NSCLC,平均年龄为68岁,ECOG <或= 2的患者(男42例,女6例)。他们每3 w分次服用顺铂(30 mg / sqm,第1-3天)和口服依托泊苷(50 mg,第1-15天),并分为五个接受不同贝伐单抗剂量(0; 2.5; 5; 7.5;和在第3天服用10毫克/千克)。结论:贝伐单抗与剂量/密集化疗方案的组合产生中等安全性,但显示出显着的抗血管生成和抗肿瘤活性。

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