Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. intergroup/RTOG 9704 phase III trial

William F. Regine, Kathryn A. Winter, Ross Abrams, Howard Safran, John P. Hoffman, Andre Konski, Al B Benson III, John S. MacDonald, Tyvin A. Rich, Christopher G. Willett

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Abstract

Background: The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial. Methods: After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m2/day, and gemcitabine was provided at 1000 mg/m2 weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head. Results: Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22% with gemcitabine versus 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28% of patients versus distant relapse in 73%. Conclusions: The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥70% of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine.

Original languageEnglish (US)
Pages (from-to)1319-1326
Number of pages8
JournalAnnals of surgical oncology
Volume18
Issue number5
DOIs
StatePublished - May 1 2011

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gemcitabine
Fluorouracil
Adenocarcinoma
Drug Therapy
Survival
Recurrence
Neoplasms

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Regine, William F. ; Winter, Kathryn A. ; Abrams, Ross ; Safran, Howard ; Hoffman, John P. ; Konski, Andre ; Benson III, Al B ; MacDonald, John S. ; Rich, Tyvin A. ; Willett, Christopher G. / Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma : 5-year analysis of the U.S. intergroup/RTOG 9704 phase III trial. In: Annals of surgical oncology. 2011 ; Vol. 18, No. 5. pp. 1319-1326.
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title = "Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. intergroup/RTOG 9704 phase III trial",
abstract = "Background: The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial. Methods: After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m2/day, and gemcitabine was provided at 1000 mg/m2 weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head. Results: Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22{\%} with gemcitabine versus 17.1 months and 18{\%} with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28{\%} of patients versus distant relapse in 73{\%}. Conclusions: The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥70{\%} of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine.",
author = "Regine, {William F.} and Winter, {Kathryn A.} and Ross Abrams and Howard Safran and Hoffman, {John P.} and Andre Konski and {Benson III}, {Al B} and MacDonald, {John S.} and Rich, {Tyvin A.} and Willett, {Christopher G.}",
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Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma : 5-year analysis of the U.S. intergroup/RTOG 9704 phase III trial. / Regine, William F.; Winter, Kathryn A.; Abrams, Ross; Safran, Howard; Hoffman, John P.; Konski, Andre; Benson III, Al B; MacDonald, John S.; Rich, Tyvin A.; Willett, Christopher G.

In: Annals of surgical oncology, Vol. 18, No. 5, 01.05.2011, p. 1319-1326.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma

T2 - 5-year analysis of the U.S. intergroup/RTOG 9704 phase III trial

AU - Regine, William F.

AU - Winter, Kathryn A.

AU - Abrams, Ross

AU - Safran, Howard

AU - Hoffman, John P.

AU - Konski, Andre

AU - Benson III, Al B

AU - MacDonald, John S.

AU - Rich, Tyvin A.

AU - Willett, Christopher G.

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Background: The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial. Methods: After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m2/day, and gemcitabine was provided at 1000 mg/m2 weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head. Results: Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22% with gemcitabine versus 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28% of patients versus distant relapse in 73%. Conclusions: The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥70% of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine.

AB - Background: The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial. Methods: After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m2/day, and gemcitabine was provided at 1000 mg/m2 weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head. Results: Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22% with gemcitabine versus 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28% of patients versus distant relapse in 73%. Conclusions: The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥70% of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine.

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U2 - 10.1245/s10434-011-1630-6

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