Effect of non-anticancer drugs on prognosis of pancreatic cancer (PaC) receiving chemotherapy.

Abstract

309 Background: Non-anticancer drugs such as metformin or statin are reported to have a potential role in cancer treatment and we previously reported inhibition of renin-angiotensin system (RAS) by angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) lead to better prognosis in PaC receiving gemcitabine (Br J Cancer 103: 1644-8). The relation between diabetes (DM) with its medication and the incidence of PaC has been described but its impact on prognosis is still unclear. Methods: We retrospectively reviewed 250 pts with advanced PaC receiving chemotherapy with gemcitabine and/or S-1 between June 2001 and April 2011 with a median follow up of 9.9 months (Mo). Univariate and multivariate analyses of progression-free survival (PFS) and overall survival (OS) were performed in pts with and without DM, using age, gender, BMI, PS, stage, protocol, DM with its treatment, hypertension (HT) with its treatment, and use of statin as variables. Results: DM was diagnosed in 124 pts (49%) and was treated with insulin or insulin analogs (n = 59), sulfonylurea (n = 38), biguanide (n = 8), thiazolidinedione (n = 6), and alpha-glucosidase inhibitor (n = 5). Statin was used in 16 pts with DM and 14 pts without DM. Locally advanced disease (44% vs. 29%) and HT (44% vs. 28%) were more prevalent in pts with DM. PFS (6.3 vs. 4.9 Mo, P = 0.440) and OS (13.3 vs. 10.0 Mo, P = 0.084) was longer in pts with DM, though not significantly. Use of statin in pts with DM was associated with longer PFS (11.6 vs. 6.0 Mo, P = 0.034) and longer OS (25.4 vs. 11.3 Mo, P = 0.006), while PFS and OS did not differ by the use of statin in pts without DM. Multivariate subgroup analysis with and without DM showed metastatic disease (Hazard ratio [HR] 2.11, P = 0.001 and HR 1.57, P = 0.013), PS 0-1 (HR 0.08, P <0.001 and HR 0.21, P <0.001), use of ACEI/ARB (HR 0.60, P = 0.030 and HR 0.46, P = 0.031) as common prognostic factors for OS. Doublet chemotherapy (HR 0.48, P = 0.007) and use of statin (HR 0.40, P = 0.010) were prognostic only in pts with DM, but any medications for DM were not significant prognostic factors. Conclusions: In our retrospective analysis, use of statin in pts with DM as well as inhibition of RAS was associated with better prognosis in pts with PaC receiving chemotherapy.