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.
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.
Authors: Joong-Won Park; Richard S Finn; Jun Suk Kim; Mark Karwal; Ruby K Li; Fuad Ismail; Melanie Thomas; Rosemarie Harris; Christine Baudelet; Ian Walters; Jean-Luc Raoul Journal: Clin Cancer Res Date: 2011-02-24 Impact factor: 12.531
Authors: Ahmed O Kaseb; Jeffrey S Morris; Manal M Hassan; Adnan M Siddiqui; E Lin; Lianchun Xiao; Eddie K Abdalla; Jean-Nicolas Vauthey; Thomas A Aloia; Sunil Krishnan; James L Abbruzzese Journal: J Clin Oncol Date: 2011-09-12 Impact factor: 44.544
Authors: Weijing Sun; Davendra Sohal; Daniel G Haller; Kristine Mykulowycz; Mark Rosen; Michael C Soulen; Millie Caparro; Ursina R Teitelbaum; Bruce Giantonio; Peter J O'Dwyer; Abraham Shaked; Rajender Reddy; Kim Olthoff Journal: Cancer Date: 2011-01-24 Impact factor: 6.860
Authors: Adrian M Jubb; Kathy D Miller; Hope S Rugo; Adrian L Harris; Dafeng Chen; James D Reimann; Melody A Cobleigh; Maike Schmidt; Virginia K Langmuir; Kenneth J Hillan; Daniel S Chen; Hartmut Koeppen Journal: Clin Cancer Res Date: 2011-01-11 Impact factor: 12.531
Authors: Avinash Kambadakone; Sam S Yoon; Tae-Min Kim; Daniel L Karl; Dan G Duda; Thomas F DeLaney; Dushyant V Sahani Journal: AJR Am J Roentgenol Date: 2015-01 Impact factor: 3.959