Phase I safety and pharmacokinetic study of bevacizumab in Chinese patients with advanced cancer.
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 distribution 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.
Wu
Jian-Yu
JY
Department of Medical Oncology, Beijing Hospital, Beijing 100730, China.
Wu
Xiao-Nan
XN
Ding
Li
L
Zhao
Yun-Bo
YB
Ai
Bin
B
Li
Yang
Y
Hu
Xin
X
Cheng
Gang
G
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D044466:Asian People; D000068258:Bevacizumab; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab