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



To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting.



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.



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.



Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate.



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.



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.



clinicaltrials.gov Identifier: NCT01821612.
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston.
Matthew H G
MH
Katz
Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, Minnesota.
Qian
Q
Shi
Department of Surgery, University of Cincinnati, Cincinnati, Ohio.
Syed A
SA
Ahmad
Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland.
Joseph M
JM
Herman
Department of Medical Oncology, NorthShore University HealthSystem, University of Chicago, Chicago, Illinois.
Robert de W
Rde W
Marsh
Department of Medical Oncology, University of California-San Francisco, San Francisco.
Eric
E
Collisson
Department of Radiology, Columbia University, New York, New York.
Lawrence
L
Schwartz
Department of Pathology, Ohio State University, Columbus.
Wendy
W
Frankel
Department of Surgery, University of Louisville, Louisville, Kentucky.
Robert
R
Martin
Department of Surgery, Ochsner Medical Center, New Orleans, Louisiana.
William
W
Conway
Department of Surgery, Mayo Clinic, Rochester, Minnesota.
Mark
M
Truty
Department of Medical Oncology, University of Chicago, Chicago, Illinois.
Hedy
H
Kindler
Department of Surgery, University of California, San Diego.
Andrew M
AM
Lowy
Department of Medical Oncology, Ohio State University, Columbus.
Tanios
T
Bekaii-Saab
Department of Medical Oncology, Karmanos Cancer Center, Detroit, Michigan.
Philip
P
Philip
Department of Surgery, NorthShore University HealthSystem, University of Chicago, Chicago, Illinois.
Mark
M
Talamonti
Department of Medical Oncology, Vanderbilt University, Nashville, Tennessee.
Dana
D
Cardin
Department of Medical Oncology, University of Wisconsin-Madison, Madison, Wisconsin.
Noelle
N
LoConte
Department of Surgery, Wake Forest University, Winston Salem, North Carolina.
Perry
P
Shen
Department of Surgery, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
John P
JP
Hoffman
Department of Medical Oncology, University of California-San Francisco, San Francisco.
Alan P
AP
Venook
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine / Q000008:administration & dosage; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D000072662:Margins of Excision; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D011446:Prospective Studies; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D015996:Survival Rate
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin