Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer alliance for clinical trials in oncology trial A021101

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 & 1 others Alan P. Venook

Research output: Contribution to journalArticle

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 (85mg/m2 of oxaliplatin, 180mg/m2 of irinotecan hydrochloride, 400mg/m2 of leucovorin calcium, and then 2400mg/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 (825mg/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.

Original languageEnglish (US)
Article numbere161137
JournalJAMA Surgery
Volume151
Issue number8
DOIs
StatePublished - Aug 1 2016

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Pancreatic Neoplasms
Clinical Trials
Pancreatectomy
Therapeutics
oxaliplatin
irinotecan
Feasibility Studies
Capecitabine
Radiation Dosage
Leucovorin
Residual Neoplasm
Fluorouracil
Quality Control
Multicenter Studies
Blood Vessels
Retrospective Studies
Biopsy
Safety

ASJC Scopus subject areas

  • Surgery

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Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer alliance for clinical trials in oncology trial A021101. / Katz, Matthew H G; Shi, Qian; Ahmad, Syed A.; Herman, Joseph M.; Marsh, Robert De W; Collisson, Eric; Schwartz, Lawrence; Frankel, Wendy; Martin, Robert; Conway, William; Truty, Mark; Kindler, Hedy; Lowy, Andrew M.; Bekaii-Saab, Tanios; Philip, Philip; Talamonti, Mark; Cardin, Dana; LoConte, Noelle; Shen, Perry; Hoffman, John P.; Venook, Alan P.

In: JAMA Surgery, Vol. 151, No. 8, e161137, 01.08.2016.

Research output: Contribution to journalArticle

Katz, MHG, Shi, Q, Ahmad, SA, Herman, JM, Marsh, RDW, Collisson, E, Schwartz, L, Frankel, W, Martin, R, Conway, W, Truty, M, Kindler, H, Lowy, AM, Bekaii-Saab, T, Philip, P, Talamonti, M, Cardin, D, LoConte, N, Shen, P, Hoffman, JP & Venook, AP 2016, 'Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer alliance for clinical trials in oncology trial A021101', JAMA Surgery, vol. 151, no. 8, e161137. https://doi.org/10.1001/jamasurg.2016.1137
Katz, Matthew H G ; Shi, Qian ; Ahmad, Syed A. ; Herman, Joseph M. ; Marsh, Robert De W ; Collisson, Eric ; Schwartz, Lawrence ; Frankel, Wendy ; Martin, Robert ; Conway, William ; Truty, Mark ; Kindler, Hedy ; Lowy, Andrew M. ; Bekaii-Saab, Tanios ; Philip, Philip ; Talamonti, Mark ; Cardin, Dana ; LoConte, Noelle ; Shen, Perry ; Hoffman, John P. ; Venook, Alan P. / Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer alliance for clinical trials in oncology trial A021101. In: JAMA Surgery. 2016 ; Vol. 151, No. 8.
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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 (85mg/m2 of oxaliplatin, 180mg/m2 of irinotecan hydrochloride, 400mg/m2 of leucovorin calcium, and then 2400mg/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 (825mg/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.",
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T1 - Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer alliance for clinical trials in oncology trial A021101

AU - Katz, Matthew H G

AU - Shi, Qian

AU - Ahmad, Syed A.

AU - Herman, Joseph M.

AU - Marsh, Robert De W

AU - Collisson, Eric

AU - Schwartz, Lawrence

AU - Frankel, Wendy

AU - Martin, Robert

AU - Conway, William

AU - Truty, Mark

AU - Kindler, Hedy

AU - Lowy, Andrew M.

AU - Bekaii-Saab, Tanios

AU - Philip, Philip

AU - Talamonti, Mark

AU - Cardin, Dana

AU - LoConte, Noelle

AU - Shen, Perry

AU - Hoffman, John P.

AU - Venook, Alan P.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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 (85mg/m2 of oxaliplatin, 180mg/m2 of irinotecan hydrochloride, 400mg/m2 of leucovorin calcium, and then 2400mg/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 (825mg/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.

AB - 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 (85mg/m2 of oxaliplatin, 180mg/m2 of irinotecan hydrochloride, 400mg/m2 of leucovorin calcium, and then 2400mg/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 (825mg/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.

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