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Phase I safety and pharmacokinetic study of bevacizumab in Chinese patients with advanced cancer

摘要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.

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分类号 R5
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DOI 10.3760/cma.j.issn.0366-6999.2010.07.025
发布时间 2010-06-02(万方平台首次上网日期,不代表论文的发表时间)
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中华医学杂志(英文版)

中华医学杂志(英文版)

2010年123卷7期

901-906页

SCIMEDLINEISTICCSCDCABP

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