Potentially curative combination of TGF-b1 inhibitor losartan and FOLFIRINOX (FFX) for locally advanced pancreatic cancer (LAPC): R0 resection rates and preliminary survival data from a prospective phase II study.

Abstract

4116Background: FFX is under study in LAPC for its potential for curative resection, but the downstaging rate remains low. Preclinical data suggest that inhibition of the renin-angiotensin system with losartan reduces TGF-b1 activity, enhancing intratumoral penetration of chemotherapy by remodeling desmoplasia and improving perfusion. This study investigated the R0 resection rate of FFX/losartan in LAPC. Methods: LAPC pts (per NCCN criteria), ECOG PS 0-1 were enrolled in a single institution NCI-sponsored phase II study (NCT01821729). Pts received 8 cycles FFX/losartan. If the tumor was radiographically resectable after chemotherapy, pts received short-course chemoradiation (CRT) in 5 fractions (protons 25 GyE, capecitabine 825 mg/m2 bid). If the tumor still abutted vasculature, pts received CRT to 50.4 Gy with a vascular boost to 58.8 Gy. Primary endpoint was R0 resection rate. Secondary endpoints were mPFS, mOS and circulating biomarkers of losartan activity. Results: 50 pts enrolled from 8/2013 to 7/20...