ACEIs/ARBs to improve survival in advanced gastric cancer patients receiving S-1 plus cisplatin.

174 Background: Gastric cancer is heterogeneous disease and male predominant incidence is recognized across the world. Interactions between tumor cells and microenvironments, such as cancer-associated fibroblasts (CAFs) and M2 macrophage, play an important role in cancer progression and CAFs and M2 macrophage predict worse outcomes in several types of cancer. Angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) are widely used in cardiovascular disease because these drugs reduced cardiovascular events via inhibiting fibroblasts and inflammation. Moreover these drugs improved survival in advanced pancreatic cancer gemcitabine (Br J Cancer, Nakai, 2010). Given that CAFs and M2 macrophage are associated worse outcomes and ACEIs/ARBs may inhibit these factors, we hypothesized that these drugs may improve survival in advanced gastric cancer. Methods: Two-hundred and twenty advanced gastric cancer patients were enrolled between Jan. 2007 and Dec. 2011. These patients were received S-1 plus cisplatin (SP) as the first-line therapy in our institute. We retrospectively analyzed whether ACEIs/ARBs could predict better survival. Primary endpoint was overall survival (OS) and endpoint was estimated using by Kaplan-Meier methods and compared by the log-rank test. Results: Median age was 61 years old and 68.1% of the patients were male. Eighteen of 220 patients took ACEIs and/or ARBs. No significant difference was shown in patient characteristics between two groups. Median survival time (MST) of all patients was 416 days. There was marginal differences between two groups; MST in ACEI/ARB group was 763 days and 412 days in non-ACEI/ARB group, respectively (HR, 0.59 ; 95% CI 0.34-1.05 ; P=0.071). After analyzing according to gender, MST in male was 997 days in ACEI/ARB group vs. 412 days in non-ACEI/ARB group (HR, 0.42 ; 95% CI 0.18-0.97 ; P=0.037); however, no significant difference was found in female (HR, 0.84 ; 95% CI 0.38-1.86 ; P=0.67). Conclusions: ACEIs/ARBs may have a favorable effect in gastric cancer; however, gender difference may be involved in their efficacy. Further clinical validations and molecular correlation analyses are warranted.