Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer

Abstract

IMPORTANCE Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. OBJECTIVE To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50–76 years]; 55% female). Patients registered between May 29, 2013, and February 7,2014. INTERVENTIONS Patients received modified FOLFIRINOX treatment (85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan hydrochloride, 400 mg/m2 of leucovorin calcium, and then 2400 mg/m2 of 5-fluorouracil for 4 cycles) followed by 5.5 weeks of external-beam radiation (50.4 Gy delivered in 28 daily fractions) with capecitabine (825 mg/m2 orally twice daily) prior to pancreatectomy. MAIN OUTCOMES AND MEASURES Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate. RESULTS The accrual rate of 2.6 patients per month was superior to the anticipated rate. Although 14 of the 22 patients (64% [95% CI, 41%–83%]) had grade 3 or higher adverse events, 15 of the 22 patients (68% [95% CI, 49%–88%]) underwent pancreatectomy. Of these 15 patients, 12 (80%) required vascular resection, 14 (93%) had microscopically negative margins, 5 (33%) had specimens that had less than 5% residual cancer cells, and 2 (13%) had specimens that had pathologic complete responses. The median overall survival of all patients was 21.7 months (95% CI, 15.7 to not reached) from registration. CONCLUSIONS AND RELEVANCE The successful completion of this collaborative study demonstrates the feasibility of conducting quality-controlled trials for this disease stage in the multi-institutional setting. The data generated by this study and the logistical elements that facilitated the trial's completion are currently being used to develop cooperative group trials with the goal of improving outcomes for this subset of patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01821612

Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

“…Several trials have shown that preoperative treatment of borderline resectable pancreatic adenocarcinoma can be effective and well-tolerat-ed. [148][149][150][151][152][153][154][155] Neoadjuvant therapy should preferably be administered at or coordinated through a high-volume center. Upfront resection in patients with borderline resectable disease is no longer recommended, as of the 2016 version of these guidelines.…”

Pathological complete response in pancreatic adenocarcinoma with FOLFIRINOX

“…Recently, Katz et al concluded a trial and showed that 68% of patients with borderline pancreatic cancer who underwent therapy with modified FOLFIRINOX regimen followed by capecitabine-based chemoradiation underwent successful surgical resection. The median survival for these patients were 21.7 months (95% CI 15.7 to not reached) 12. Similarly, Rombouts et al reported pCR in 7% of resected specimen after the patients were initially diagnosed with locally advanced pancreatic cancer and underwent therapy with either FOLFIRINOX alone, modified FOLFIRINOX or in combination with radiation therapy 13…”

Preoperative Chemoradiation for Borderline Resectable Pancreatic Cancer: The New Standard?

“…Furthermore, the technical conduct of surgery, including the extent of vascular dissection and lymphadenectomy, was mandated by protocol. These design elements are critical to the interpretation of investigations of preoperative therapy for pancreatic cancer, particularly in the multi-institutional setting [6, 7]. …”