Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer
Year: 2016
Type: article
Study design: Clinical Trial
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.
Source: JAMA Surgery
Authors: Matthew H. G. Katz, Qian Shi, Syed A. Ahmad, Joseph M. Herman, Robert de W. Marsh, Eric Collisson, Lawrence Schwartz, Wendy Frankel, Robert Martin, William Conway, Mark Truty, Hedy Kindler, Andrew M. Lowy, Tanios Bekaii-Saab, Philip Philip, Mark Talamonti, Dana Cardin, Noelle LoConte, Perry Shen, John P. Hoffman, Alan P. Venook
Institutions: The University of Texas MD Anderson Cancer Center, Mayo Clinic, Alliance for Clinical Trials in Oncology, University of Cincinnati, Johns Hopkins University, Endeavor Health, University of Chicago, University of California, San Francisco, Columbia University, The Ohio State University, University of Louisville, Ochsner Medical Center, University of California San Diego, The Barbara Ann Karmanos Cancer Institute, Vanderbilt University, University of Wisconsin–Madison, Wake Forest University Health Sciences, Wake Forest University, Fox Chase Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Alliance Statistics and Data Management Center, ECOG-ACRIN Network Group Operations Center, G260759372, Johns Hopkins University NCTN Lead Academic Site Program, NCI National Clinical Trials Network-Network Lead Academic Participating Site, SWOG Network Group Operations Center of the NCTN, NCI National Clinical Trials Network-Network Lead Academic Participating Sites, UT MD Anderson Cancer Center Network Lead Academic Participating Site (LAP) UG1, Naional Cancer Institute, Naitonal Clinical Trials Network U10 Lead Academic Site, UT MD Anderson Cancer Center Network Lead Academic Participating Site (LAP), NCI, National Clinical Trials Network Lead Academic Participating Site (LAPS) UG1, G6701990775, OSU as Network Lead Academic Participating Site for the NCI NCTN, NCTN Lead Academic Participating Site at Dana-Farber/Partners Cancer Care, Johns Hopkins University NCTN Lead Academic Site Program, SWOG Community Clinical Oncology Program Research Base, Ochsner NCI Community Oncology Research Program, Vanderbilt Network Lead Academic Participating Site for the NCTN, Alliance for Clinical Trials in Oncology Operations Center, Vanderbilt Network Lead Academic Participating Site for the NCTN, National Clinical Trials Network Research at the University of Wisconsin, CANCER CENTER SUPPORT GRANT
OpenAlex ID: W2409856225