Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: A pilot study
1 Division 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
2 Departments 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
3 Department 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
4 Genentech, Inc., 1 DNA Way, MS 46-3A, South San Francisco, CA, USA
5 Department 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
BMC Cancer 2012, 12:16 doi:10.1186/1471-2407-12-16Published: 14 January 2012
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.
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.
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.
IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE, and appeared to diminish neovessel formation at week 14.