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BMC Cancer. 2012; 12: 16.
Published online Jan 14, 2012. doi:  10.1186/1471-2407-12-16
PMCID: PMC3292503
Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: A pilot study
Carolyn D Britten,corresponding author1 Antoinette S Gomes,2 Zev A Wainberg,1 David Elashoff,3 Rafael Amado,1 Yan Xin,4 Ronald W Busuttil,5 Dennis J Slamon,1 and Richard S Finn1
1Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, 2825 Santa Monica Blvd., Suite 200, Santa Monica, CA 90404-2429, USA
2Departments of Medicine and Radiologic Science, David Geffen School of Medicine at the University of California, Los Angeles, Box 957437, Ronald Reagan Medical Center, Suite 2125, Los Angeles, CA 90095-7437, USA
3Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, 10940 Wilshire Blvd., Suite 1223, Los Angeles, CA 90095-7362, USA
4Genentech, Inc., 1 DNA Way, MS 46-3A, South San Francisco, CA, USA
5Department of Surgery, Chairman's Office, David Geffen School of Medicine at the University of California, Los Angeles, Box 957430, 757 Westwood Plaza, Suite 8236, Los Angeles, CA 90095-7430, USA
corresponding authorCorresponding author.
Carolyn D Britten: cbritten/at/mednet.ucla.edu; Antoinette S Gomes: agomes/at/mednet.ucla.edu; Zev A Wainberg: zwainberg/at/mednet.ucla.edu; David Elashoff: delashoff/at/mednet.ucla.edu; Rafael Amado: rgamado/at/comcast.net; Yan Xin: xin.yan/at/gene.com; Ronald W Busuttil: rbusuttil/at/mednet.ucla.edu; Dennis J Slamon: dslamon/at/mednet.ucla.edu; Richard S Finn: rfinn/at/mednet.ucla.edu
Received June 28, 2011; Accepted January 14, 2012.
Abstract
Background
Stimulation of vascular endothelial growth factor (VEGF) has been observed following transarterial chemoembolization (TACE) in hepatocellular cancer (HCC) and may contribute to tumor regrowth. This pilot study examined whether intravenous (IV) bevacizumab, a monoclonal antibody against VEGF, could inhibit neovessel formation after TACE.
Methods
30 subjects with HCC undergoing TACE at a single academic institution were randomized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE (TACE-BEV arm) or observation (TACE-O arm). Angiography was performed with TACE at day 8, and again at weeks 10 and 14. Repeat TACE was performed at week 14 if indicated. TACE-BEV subjects were allowed to continue bevacizumab beyond week 16. TACE-O subjects were allowed to cross-over to bevacizumab at week 16 in the setting of progressive disease. The main outcome measure was a comparison of neovessel formation by serial angiography. Secondary outcome measures were progression free survival (PFS) at 16 weeks, overall survival (OS), bevacizumab safety, and an analysis of VEGF levels before and after TACE with and without bevacizumab.
Results
Among the 30 subjects enrolled, 9 of 15 randomized to the TACE-O arm and 14 of 15 randomized to the TACE-BEV arm completed all 3 angiograms. At week 14, 3 of 9 (33%) TACE-O subjects and 2 of 14 (14%) TACE-BEV subjects demonstrated neovascularity. The PFS at 16 weeks was 0.19 in the TACE-O arm and 0.79 in the TACE-BEV arm (p = 0.021). The median OS was 61 months in the TACE-O arm and 49 months in the TACE-BEV arm (p = 0.21). No life-threatening bevacizumab-related toxicities were observed. There were no substantial differences in bevacizumab pharmacokinetics compared to historical controls. Bevacizumab attenuated the increase in VEGF observed post-TACE.
Conclusions
IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE, and appeared to diminish neovessel formation at week 14.
Trial registration
ClinicalTrials.gov NCT00049322.
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