Oxaliplatin, irinotecan, and PK-adjusted 5-fluorouracil within a multidisciplinary approach in patients with locally advanced pancreatic cancer (LAPC): Preliminary results.

Abstract

356 Background: Neoadjuvant therapy is an increasingly used approach in LAPC patients (pts) but the optimal sequence remains to be defined. We evaluated the feasibility and efficacy of induction chemotherapy (ICT) with pharmacokinetic (PK) monitoring, chemo-radiotherapy (CRT) and surgery. Methods: Borderline resectable and unresectable LAPC pts with EUS stages T3-4/N+ were included. Pts were planned to receive 4 cycles of biweekly ICT with Oxalipatin (85mg/m²), Leucovorin (400mg/m²), Irinotecan (150mg/m²) and 5-FU (initial dose of 3200mg/m² in 46h and then tailored according to PK monitoring to reach an area under the curve (AUC) between 25-30 mg·h·L-1.) After ICT, pts with no progressive disease received CRT (50.4 Gy, daily concurrent Capecitabine and weekly Oxaliplatin). Surgery was planned 4 to 6 weeks after the completion of CRT. Pathological response was graded according to the CAP classification. Toxicity was recorded according to the NCI-CTCAE 4.0. Results: From November 2011 to February 2013, 13 LAPC treatment-naïve (M/F: 11/2) pts were enrolled (T4; 30.8%, N+; 61.5%, 8 borderline resectable, 5 unresectable due to celiac abutment (2 pts), SMA and celiac encasement (1 pt), unreconstructible SMV and portal occlusion (2 pts). Median age was 63. During ICT, 5- FU dose had to be increased from baseline in 30.7% pts. Grade 3-4 ICT-related toxicities were neutropenia (6 pts) and diarrhea (1 pt). During CRT, grade 3 toxicity included neutropenia (2 pts), thrombocytopenia (1 pt), diarrhea (1 pt), asthenia (1 pt) and mucositis (1 pt); three pts required hospital admission in hospital. Twelve pts completed the whole neoadjuvant program. Ten pts proceeded to surgery with an R0 resection rate of 76.9%. Pathological response was CAP 0 (no viable cells) and CAP 1 (small groups of cancer cells) in 20% and 50% of pts, respectively; ypT0 and ypN0 rates were 20 and 60%. After a median follow-up of 12 months, the 12-month actuarial median PFS and OS were 80% and 75%, respectively. Conclusions: This neoadjuvant strategy seems feasible and promising although a longer follow-up is required. 5-FU PK modulation may contribute to a better therapeutic index.