Early antiangiogenic activity of bevacizumab evaluated by computed tomography perfusion scan in patients with advanced hepatocellular carcinoma.
BACKGROUND
Hepatocellular carcinoma (HCC) is a highly vascularized tumor with a poor prognosis. In a phase II study that combined bevacizumab with gemcitabine and oxaliplatin in advanced HCC, we examined computed tomography perfusion (CTp) scan parameters as surrogate markers of angiogenesis after bevacizumab administration.


METHODS
HCC patients received bevacizumab alone i.v. at 10 mg/kg on day 1 during cycle 1. CTp scanning was performed at baseline and days 10-12 to assess changes in tissue blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface area product (PS).


RESULTS
Compared with baseline, a significant decrease in the estimated tumor perfusion parameters including BF, BV, and PS and an increase in MTT were seen on days 10-12 following bevacizumab administration alone. Patients with progressive disease had lower baseline MTT values and a higher percent increase following bevacizumab administration than those with stable disease or partial responses.


CONCLUSIONS
Bevacizumab induced a significant decrease in tumor BF, BV, and PS and an increase in MTT by CTp scan in HCC. Baseline and percent change in MTT following bevacizumab administration correlated with clinical outcome, whereas BF, BV, and PS did not.
Zhu
Andrew X
AX
Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA. azhu@partners.org
Holalkere
Nagaraj S
NS
Muzikansky
Alona
A
Horgan
Kerry
K
Sahani
Dushyant V
DV
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D018450:Disease Progression; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D011379:Prognosis; D013997:Time Factors; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome; D000093542:Gemcitabine
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000093542:Gemcitabine