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Original Investigation
August 17, 2016

Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101

Author Affiliations
  • 1Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston
  • 2Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, Minnesota
  • 3Department of Surgery, University of Cincinnati, Cincinnati, Ohio
  • 4Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland
  • 5Department of Medical Oncology, NorthShore University HealthSystem, University of Chicago, Chicago, Illinois
  • 6Department of Medical Oncology, University of California–San Francisco, San Francisco
  • 7Department of Radiology, Columbia University, New York, New York
  • 8Department of Pathology, Ohio State University, Columbus
  • 9Department of Surgery, University of Louisville, Louisville, Kentucky
  • 10Department of Surgery, Ochsner Medical Center, New Orleans, Louisiana
  • 11Department of Surgery, Mayo Clinic, Rochester, Minnesota
  • 12Department of Medical Oncology, University of Chicago, Chicago, Illinois
  • 13Department of Surgery, University of California, San Diego
  • 14Department of Medical Oncology, Ohio State University, Columbus
  • 15Department of Medical Oncology, Karmanos Cancer Center, Detroit, Michigan
  • 16Department of Surgery, NorthShore University HealthSystem, University of Chicago, Chicago, Illinois
  • 17Department of Medical Oncology, Vanderbilt University, Nashville, Tennessee
  • 18Department of Medical Oncology, University of Wisconsin–Madison, Madison, Wisconsin
  • 19Department of Surgery, Wake Forest University, Winston Salem, North Carolina
  • 20Department of Surgery, Fox Chase Cancer Center, Philadelphia, Pennsylvania
JAMA Surg. 2016;151(8):e161137. doi:10.1001/jamasurg.2016.1137

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