Phase I safety and pharmacokinetic study of bevacizumab in Chinese patients with advanced cancer
Phase I safety and pharmacokinetic study of bevacizumab in Chinese patients with advanced cancer
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DOI：
10.3760/cma.j.issn.0366-6999.2010.07.025
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发表时间：
2010-04-05
影响因子：
6.1
通讯作者：
Cheng Gang
中科院分区：
文献类型：
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作者：
Wu Jian-yu;Wu Xiao-nan;Cheng Gang
背景贝伐单抗是一种人源化重组血管内皮生长因子（VEGF）单克隆抗体，能特异性结合VEGF，抑制肿瘤细胞生长、增殖和转移。我们的目的是调查贝伐单抗在中国晚期cancer.Methods患者的安全性和药代动力学的39例中国转移性或复发性癌症患者既往治疗失败的贝伐单抗的I期研究纳入。贝伐珠单抗通过计算泵以5 mg/kg至15 mg/kg的剂量在90分钟内输注。患者接受了系列药代动力学评价。接受至少一次贝伐单抗输注的患者被纳入安全性研究。1例患者在3次输注后因3级蛋白尿退出。可能与研究药物相关的常见不良事件为蛋白尿（17/39，43.6%），高血压（13/39，33.3%），牙龈出血鼻出血（6/39，15.4%）、咽部炎症（6/39，15.4%）、疲劳（6/39，15.4%）和口腔炎（4/39，10.3%）。贝伐珠单抗的药代动力学在5 mg/kg q2 w-10 mg/kg q2 w和15 mg/kg q3 w范围内呈线性。在5、10和15 mg/kg单次和多次给药后，CL（清除率）、Vd（消除时的分布容积）和Vss（稳态时的分布容积）相似。未观察到非预期不良事件。药代动力学无种族差异。中华医学杂志2010;123（7）：901-906
Background bevacizumab is a humanized recombinant vascular endothelial growth factor (VEGF) monoclonal antibody, which specifically binds to VEGF and inhibits tumor cell growth, proliferation and metastasis. We aimed to investigate the safety and pharmacokinetics of bevacizumab in Chinese patients with advanced cancer.Methods Thirty-nine Chinese patients with metastatic or relapsed cancers who failed prior therapy were enrolled in this phase I study of bevacizumab. Bevacizumab was infused by a calculated pump at doses from 5 mg/kg to 15 mg/kg in 90 minutes. Patients underwent serial pharmacokinetic evaluations. Patients that received at least one infusion of bevacizumab were included in the safety study.Results Thirty-five patients finished all 5 infusions following protocol. One patient withdrew after 3 infusions due to grade 3 proteinuria. Common adverse events possibly related to the study drug were proteinuria (17/39, 43.6%), hypertension (13/39, 33.3%), gingival bleeding (7/39, 17.9%), epistaxis (6/39, 15.4%), pharyngeal inflammation (6/39, 15.4%), fatigue (6/39, 15.4%) and stomatitis (4/39, 10.3%). Bevacizumab pharmacokinetics was linear within the range of 5 mg/kg q2w-10 mg/kg q2w and 15 mg/kg q3w. CL (clearance), Vd (volume of distribution at elimination) and Vss (volume of diatribution at steady state) were similar after single and multiple doses at 5, 10 and 15 mg/kg.Conclusions Bevacizumab is well tolerated in Chinese patients. No unexpected adverse events were observed. There is no racial difference in the pharmacokinetics. Chin Med J 2010;123(7):901-906