Prognostic effect of angiotensin-converting-enzyme inhibitors in HCC patients treated with sorafenib.

Abstract

328 Background: Experimental studies indicated that angiotensin-converting-enzyme inhibitors (ACEs) or angiotensin receptor blockers (ARBs) has a role in reducing malignant changes of the liver and may significantly improve the mortality in patients with other cancers. However it is not known whether ACE and ARB inhibitors may have prognostic impact on HCC survival outcome. We aimed at evaluating the role of ACE inhibitors and ARB blockers on the prognosis of HCC patients who have been treated by Nexavar (sorafenib). Methods: Using resources of our case-control study at MD Anderson, total of 187 (males, 76.5%; females, 23.5%) pathologically confirmed HCC had been treated by sorafenib. The overall mean age (±SD) was 62.5years ± 9.6. The majority of patients were Caucasians (62.6%) who were diagnosed at TNM stage III and IV (79.2%). Total of 89 (47.6%) patients had no evidence of hepatitis C virus (HCV) or hepatitis B virus (HBV). Median survival was calculated using Kaplan Meier product-limit method and survival rates were compared using the log rank test. Cox proportional hazards model was used to estimate the univariate and multivariate Hazard Risk Ratios (HRR) and 95% Confidence Interval (CI). Results: The overall median survival of HCC patients was 19.9 months (95% CI, 16.1-23.6). Intake of ACEs or ARBs inhibitors was reported in 94 patients (50.3%). We observed significant difference in overall median survival (months) between patients who had ACE/ARB inhibitors versus those who did not, median survival (95% CI) were 21.5 (17.1-25.8) and 14.6 (12.4-16.7), respectively, p=0.04. After adjustment for HCC prognostic factors and demographic factors, we observed 30% reduction in HCC mortality among those who received ACEs/ARBs inhibitors, the estimated HR was 0.7 (95% CI, 0.4-1), p=0.05. Conclusions: Our results may indicate that HCC patients under anti-angiogenic therapy (sorafenib) and have been under anti-hypertensive therapy like ACE/ARB may assist in depleting the collagen and may improve host matrix and tumor microenvironment to enhance drug delivery. Future analysis in a larger sample is warranted