Phase Ib safety and pharmacokinetic study of volociximab, an anti-α5β1 integrin antibody, in combination with carboplatin and paclitaxel in advanced non-small-cell lung cancer
Phase Ib safety and pharmacokinetic study of volociximab, an anti-α5β1 integrin antibody, in combination with carboplatin and paclitaxel in advanced non-small-cell lung cancer
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DOI：
10.1093/annonc/mds281
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发表时间：
2013-01-01
影响因子：
50.5
通讯作者：
Belani, C. P.
中科院分区：
文献类型：
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作者：
Besse, B.;Tsao, L. C.;Belani, C. P.
这项 Ib 期研究评估了 volociximab（一种抗 α 5 β 1 整联蛋白抗体）与卡铂（Eli Lilly and Co.，印第安纳波利斯，印第安纳州）和紫杉醇 (Taxol) 联合治疗晚期、未经治疗的非小细胞肺癌 (NSCLC)。三个队列接受了 volociximab（10、20 或 30 mg/kg）治疗，治疗时间长达 六个为期 3 周的周期与卡铂-紫杉醇化疗相结合，并继续作为疾病稳定 (SD) 或好转患者的维持治疗。评估了剂量限制性毒性作用、不良事件 (AE)、药代动力学和抗沃洛昔单抗抗体。最大耐受剂量未达到最大计划剂量 30 mg/kg。在 29 名接受伏洛昔单抗治疗的患者中，最常见的 3 级以上 AE 是中性粒细胞减少症 (24%)、低钠血症 (17%) 和疲劳 (10%)。三名患者出现了与伏洛昔单抗相关的严重 AE。没有观察到出血。在 33 名入组患者中，8 名 (24%) 获得部分缓解，17 名 (52%) 出现 SD。中位无进展生存期为 6.3 个月（95% 置信区间 5.5-8.1）。六个周期的治疗后，血管生成或转移的潜在生物标志物水平降低。沃洛昔单抗联合卡铂和紫杉醇通常耐受性良好，并显示出对晚期 NSCLC 疗效的初步证据。
This phase Ib study evaluated volociximab, an anti-alpha 5 beta 1 integrin antibody, in combination with carboplatin (Eli Lilly and Co., Indianapolis, IN) and paclitaxel (Taxol) in advanced, untreated non-small-cell lung cancer (NSCLC).Three cohorts were treated with volociximab (10, 20, or 30 mg/kg) for up to six 3-week cycles in combination with carboplatin-paclitaxel chemotherapy and continued as maintenance therapy for patients with stable disease (SD) or better. Dose-limiting toxic effects, adverse events (AEs), pharmacokinetics, and anti-volociximab antibodies were assessed.A maximum tolerated dose was not reached up to the maximum planned dose of 30 mg/kg. In 29 patients who received volociximab, the most common grade >= 3 AEs were neutropenia (24%), hyponatremia (17%), and fatigue (10%). Three patients experienced volociximab-related serious AEs. No hemorrhages were observed. Of 33 patients enrolled, 8 (24%) achieved a partial response and 17 (52%) had SD. The median progression-free survival was 6.3 months (95% confidence interval 5.5-8.1). Levels of potential biomarkers of angiogenesis or metastasis were reduced following six cycles of treatment.Volociximab combined with carboplatin and paclitaxel was generally well-tolerated and showed preliminary evidence of efficacy in advanced NSCLC.