Background: Results from the phase III PRODIGE 4/ACCORD 11 trial provided one of current standard regimens for advanced pancreatic cancer (PC), consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX), which has superior response rate (RR) and survival benefit even with severe toxicity (Thierry C, et al. N Engl J Med 2011;364:1817-1825). There are several reports on the correlation between early tumor shrinkage (ETS) or depth of response (DpR) and survival in chemotherapies for colorectal cancer; however, few studies have investigated it in PC. We therefore analyzed retrospectively whether the ETS will predict outcomes in pts with PC treated with FOLFIRINOX therapy. Methods: Advanced PC pts with ECOG PS of 0 or 1, who received FOLFIRINOX as 1st- or 2nd-line treatment between November 2012 and July 2015 in 3 institutes of Showa University were included in this analysis. ETS was defined as a reduction ≥ 20% of target lesions’ diameters measured at 8 weeks from treatment start. We evaluated the association of ETS with progression-free survival (PFS) and overall survival (OS) but also addressed the correlation between outcomes and DpR, which was percentage of maximal tumor shrinkage observed at the nadir diameter compared with baseline. Results: Fifty-nine PC pts with median age of 63 (range 34-76) years and males of 68% were enrolled: 80% of pts had metastatic disease. In the population, RR, median PFS, and OS were 28%, 5.4 months, and 10.7 months, respectively. Among 46 (78%) evaluable pts for the ETS, 12 (26%) pts experienced ETS. The PFS was significantly longer in pts with ETS compared to pts with no ETS (9.0 vs. 4.2 months, HR 0.43, 95%CI 0.17-0.96, log-rank P= 0.045). Moreover, pts with ETS had a better OS although no statistical significance (HR 0.53, log-rank P= 0.25). Median DpR was 11.1% (from -75.7 to 100), and the correlation of DpR with clinical outcome was observed (P= 0.024 for PFS, P= 0.22 for OS). Conclusions: This retrospective analysis suggests that the early response to FOLFIRINOX treatment may predict better outcomes in pts with advanced PC. The ETS may serve as a novel predictor of prolonged survival time in PC pts treated with FOLFIRINOX.