Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer
Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer
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DOI：
10.1200/jco.2001.19.3.843
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发表时间：
2001-02-01
影响因子：
45.3
通讯作者：
Adelman, DC
中科院分区：
文献类型：
--
作者：
Gordon, MS;Margolin, K;Adelman, DC
目的：研究重组人单克隆抗体血管内皮生长因子（rhuMAb VEGF）在肿瘤患者中的安全性和药代动力学。患者和方法先前治疗失败的转移性癌症患者队列进入rhuMAb VEGF的I期试验，在第0、28、35和42天以0.1至10.0 mg/kg的剂量静脉输注90分钟。患者在第0天进行药代动力学采样，并在随后的28天内获得血清样本。在第49天和第72天进行反应评估。共25例患者，东部肿瘤合作组评分中位数为0。没有III级或IV级不良事件明确与抗体相关。有三次肿瘤相关出血。输注rhuMAb VEGF耐受性良好，无明显毒性。可能或可能与研究药物相关的I级和II级不良事件包括虚弱、头痛和恶心。药代动力学显示半衰期为21天，呈线性分布。结论：rhuMAb - VEGF在10mg /kg的剂量范围内是安全的，没有剂量限制性毒性。多次剂量的rhuMAb VEGF耐受性良好，药代动力学研究表明，0.3 mg/kg剂量的半衰期与其他人源化抗体相似。后续试验将探索rhuMAb VEGF单独和联合化疗。(C) 2001年美国临床肿瘤学会。
Purpose: We investigated the safety and pharmacokinetics of a recombinant human monoclonal antibody ta vascular endothelial growth factor (rhuMAb VEGF) in patients with cancer.Patients and Methods Cohorts of patients with metastatic cancer having failed prior therapy entered a phase I trial of rhuMAb VEGF administered by a 90-minute intravenous infusion at doses from 0.1 to 10.0 mg/kg on days 0, 28, 35, and 42. Patients underwent pharmacokinetic sampling on day 0 and had serum samples obtained during the subsequent 28 days. Response assessment was carried out on days 49 and 72.Results.. Twenty-five patients with a median Eastern Cooperative Oncology Group performance status of 0 were accrued. There were no grade III or IV adverse events definitely related to the antibody. There were three episodes of tumor-related bleeding. Infusions of rhuMAb VEGF were well tolerated without significant toxicity. Grades I and II adverse events possibly or probably related to study drug included asthenia, headache, and nausea. Pharmacokinetics revealed a linear profile with a half-life of 21 days. There were no objective responses, though 12 patients experienced stable disease over the duration of the studyConclusion: rhuMAb VEGF was safely administered without dose-limiting toxicity at doses ranging up to 10 mg/kg. Multiple doses of rhuMAb VEGF were well tolerated, and pharmacokinetic studies indicate that doses of 0.3 mg/kg have a half-life similar to that of other humanized antibodies. Subsequent trials will explore rhuMAb VEGF alone and in combination chemotherapy. (C) 2001 by American Society of Clinical Oncology.