Background: FOLFIRINOX provides clinically significant benefit in advanced PC compared to gemcitabine (Conroy et al. New Engl J Med 2011;364:1817). Despite superior efficacy, toxicities have tempered enthusiasm for FOLFIRINOX and limited its use in full doses. To assess the impact of dose attenuations on toxicity and efficacy, we reviewed our experience with FOLFIRINOX in pts with advanced PC. Methods: We performed a retrospective review of dose, toxicity, efficacy of FOLFIRINOX in all pts with locally advanced unresectable PC (LAPC) and metastatic PC (MPC) treated with FOLFIRINOX at Yale Cancer Center between 06/10 and 06/11. Dose attenuations were at the treating physician’s discretion. All pts received prophylactic pegfilgrastim. Pts were treated until progression, unacceptable toxicity, or surgical resection. Toxicities and efficacy were compared to historical data reported by Conroy. Results: 31 pts with ECOG PS 0 or 1 were treated. Pt characteristics: LAPC 15; MPC 16; median (med) age 60 yrs (range 48-78); male 11; prior chemotherapy 5 (adjuvant 3). Med number of cycles received was 6 (range 1-18). Only 5 pts received full doses of all drugs with cycle 1. Dose reductions with cycle 1 were: IRI 26 pts, OX 10 pts, bFU 10 pts, infusional FU 1 pt. b5FU was omitted in 6 pts. Med relative dose intensities were: OX 88%, IRI 64%, b-FU 57%, infusional FU 100% (compared to OX 78%, IRI 81%, and FU 82% [Conroy]). The % of pts with grade 3 or 4 toxicities was: fatigue or mucositis, 9.6%; dehydration or neutropenia 6.4%; vomiting, thromboembolism, febrile neutropenia, thrombopenia or anemia, 3.2%. Neutropenia (p<0.0001), diarrhea (p<0.03), fatigue (p<0.02) were significantly decreased compared to historical data (Conroy). Response (CR+PR) in 30 evaluable pts was 33% (1 CR, 9 PR, 14 SD, 6 PD) and similar to historical data (31.6%; p 0.21). 2 pts with LAPC underwent resection. Evaluation for OS and PFS is ongoing. Conclusions: Our findings suggest that dose attentuation of FOLFIRINOX, esp IRI and bFU, with prophylactic pegfilgrastim is associated with improved tolerability and equivalent response rate compared to full dose FOLFIRINOX in advanced PC. The impact of dose attenuations on toxicity and efficacy warrants further evaluation in both LAPC and MPC.