Primary systemic therapy in resectable pancreatic ductal adenocarcinoma using mFOLFIRINOX: A pilot study

Abstract

Background and Objectives Surgery followed by gemcitabine and/or a fluoropyrimidine is standard therapy for resectable PDAC. mFOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 Day 1, 5-FU 2400 mg/m2 × 48 h IV, peg-filgrastim 6 mg SQ day 3, every 14 days) has substantial activity in metastatic PDAC. We wished to determine the tolerability/efficacy of peri-operative mFOLFIRINOX in resectable PDAC. Methods Patients with resectable PDAC (ECOG PS 0/1) received four cycles of mFOLFIRINOX pre- and post-surgery. The primary endpoint was completion of preoperative chemotherapy plus resection. Secondary endpoints included completion of all therapy, R0 resection, treatment related toxicity, PFS, and OS. Results Twenty-one patients enrolled: median age 62 (47–78); 20/21 (95%) completed four cycles of preoperative mFOLFIRINOX; response by RECIST was 1 CR, 3 PR, 16 SD; 17/21 (81%) completed resection, 16/21 (76%) R0; 14/21 (66%) completed four cycles of postoperative mFOLFIRINOX. Grade 3 and 4 toxicity occurred in 23% and 14% patients pre-operatively, 26% and 6.0% post-operatively. Nine patients are alive with median follow-up of 27.7 (3.1–47.1) months. Conclusions PST using mFOLFIRINOX in resectable PDAC is feasible and tolerable. R0 resection rate is high and survival promising, requiring longer follow-up and larger studies for definitive assessment.

Impact of neoadjuvant therapy on postoperative outcomes after pancreaticoduodenectomy

“…Neoadjuvant therapy may also identify patients that would not benefit from surgical resection due to rapidly progressive metastatic disease . Approximately 25% of patients who undergo preoperative chemotherapy or chemoradiation for pancreatic cancer do not undergo resection due to either preoperative disease progression, decline in performance status, or extrapancreatic disease found at the time of surgery …”

“…22 Approximately 25% of patients who undergo preoperative chemotherapy or chemoradiation for pancreatic cancer do not undergo resection due to either preoperative disease progression, decline in performance status, or extrapancreatic disease found at the time of surgery. [22][23][24] Despite these potential advantages, concerns remain regarding higher rates of perioperative complications in patients undergoing neoadjuvant therapy. 11,25,26 However, existing data do not support this concern.…”

Neoadjuvant Treatment in Patients With Resectable and Borderline Resectable Pancreatic Cancer

“…A propensity score matched analysis was conducted comparing outcomes for patients who received neoadjuvant treatment before resection (n = 2005) to patients who underwent upfront resection (n = 6015). (Table 3A) (47)(48)(49). In 2016, the first prospective multicenter trial was published (ALLIANCE A021101), including 22 BRPC patients who received preoperative mFOLFIRINOX (4 cycles) followed by capecitabine-based chemoradiotherapy (50.4 Gy in 28 fractions) (47).…”

“…The median OS was 22 months. In 2018, a similar study was published to determine the tolerability and efficacy of four cycles of mFOLFIRINOX both pre-and post-operative in resectable PDAC (48). Twentyone patients were included, of whom 81% underwent a resection with an R0 resection rate of 94%.…”

Current Therapeutic Options for Pancreatic Ductal Adenocarcinoma

“…Interestingly, recent evidence suggests that toxicity of FOLFIRINOX might at least partially be improved by implementation of a modified FOLFIRINOX protocol omitting the 5-FU bolus, while potentially retaining similar efficacy [37,38]. Similarly, an innovative small single-arm phase I-II study recently provided first evidence that alternating treatment following FOLFIRINOX and gemcitabine plus nab-paclitaxel protocols (GABRINOX) might be another way of significantly reducing adverse effects of chemotherapy while potentially retaining therapeutic efficacy [39.] However, this concept as well needs further validation in controlled prospective trials.…”