Article: article from journal or magazin.
Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma
1549-490X (Electronic)1083-7159 (Linking)
Boige, ValerieMalka, DavidBourredjem, AbderrahmaneDromain, ClarisseBaey, CharlotteJacques, NathaliePignon, Jean-PierreVimond, NadegeBouvet-Forteau, NathalieDe Baere, ThierryDucreux, MichelFarace, FrancoiseengClinical Trial, Phase IIResearch Support, Non-U.S. Gov't2012/06/19 06:00Oncologist. 2012;17(8):1063-72. doi: 10.1634/theoncologist.2011-0465. Epub 2012 Jun 15.
OBJECTIVE: Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. METHODS: In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. RESULTS: The 16W-DCR was 42% (95% confidence interval, 27%-57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3-4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p </= .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p </= .04). CONCLUSION: Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation.
Adult, Aged, Aged, 80 and over, Angiogenesis Inducing Agents/blood, *Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects, Bevacizumab, Biomarkers, Pharmacological/*blood, Carcinoma, Hepatocellular/blood/*drug therapy/pathology, Disease-Free Survival, Female, Humans, Interleukin-6/blood, Interleukin-8/blood, Liver Neoplasms/blood/*drug therapy/pathology, Male, Middle Aged, Neoplasm Staging, Neoplastic Cells, Circulating/metabolism, Safety
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