Dose intensity of neoadjuvant FOLFIRINOX (FFX) in borderline and locally advanced pancreatic cancer (LAPC): A comparison to the adjuvant benchmark.

Abstract

392 Background: Optimal timing and duration of FFX for resectable, borderline resectable, and LAPC has not been established. The PRODIGE 24/CCTG PA.6 study used 12 cycles of adjuvant modified FFX (eliminating bolus 5FU, irinotecan at 150mg/m2) demonstrating superior DFS (21.6 mo) over gemcitabine (12.8 mo). However, only 48% of patients (pts) received 70% of intended chemo dosing, and 66.4% of pts completed all doses due to postoperative tolerability. We conducted total neoadjuvant therapy (TNT) studies in borderline and LAPC. (LAPC study included Losartan experimentally.) Dose intensity of TNT with FFX is compared to the benchmark adjuvant data. Methods: In this retrospective analysis, chemotherapy data were analyzed from NCT01821729 (LAPC) and NCT01591733 (Borderline). Both studies included 8 cycles of neoadjuvant FFX: b5FU 400mg/m2, CI 5U 1200mg/m2/d x 2d, oxaliplatin 85mg/m2, and irinotecan 180mg/m2. Results: 92 pts were studied: Borderline n = 43, LAPC n = 49. Sixteen of 92 (17.3%) patients discontinued chemotherapy prior to 8 cycles due to: withdrawal of consent (2), chemotherapy toxicity (6), progression (4), and disease-related complications (4). 82.6% of patients completed 8 doses. 61.4% of all bFU was given at the intended dose of 400 mg/m2. The mean relative dose intensity of b5FU (the actual cumulative dose relative to the planned cumulative dose over 8 cycles) was 72%. 65.5% of patients required a reduction in b5FU over eight cycles. Data for all chemotherapy are presented in Table 1. Overall, 71 of 92 patients (77.2%) had > 70% dose of FFX, with mean relative dose intensity of 81.2%. Among surgically resected patients, mPFS was 21.3 months in LAPC (n = 34) and 48.6 months in Borderline (n = 33). Conclusions: Compared to adjuvant therapy, dose intensity was achieved in a higher proportion of participants with TNT, utilizing a FFX regimen that included b5FU and irinotecan at 180mg/m2. PFS among resected patients reflects this highly active treatment. [Table: see text]