Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: A randomized controlled trial

William F. Regine, Kathryn A. Winter, Ross A. Abrams, Howard Safran, John P. Hoffman, Andre Konski, Al B. Benson, John S. Macdonald, Mahesh R. Kudrimoti, Mitchel L. Fromm, Michael Haddock, Paul Schaefer, Christopher G. Willett, Tyvin A. Rich

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Abstract

Context: Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil. Objective: To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. Design, Setting, and Participants: Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. Intervention: Chemotherapy with either fluorouracil (continuous infusion of 250mg/m2 per day; n=230) or gemcitabine (30-minute infusion of 1000 mg/m2 once per week; n=221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m2 per day) was the same for all patients (50.4 Gy). Main Outcome Measures: Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. Results: A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n=388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P=.09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P=.05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (P<.001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (>85%). Conclusions: The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. Trial Registration: clinicaltrials.gov Identifier: NCT00003216.

Original languageEnglish (US)
Pages (from-to)1019-1026
Number of pages8
JournalJAMA - Journal of the American Medical Association
Volume299
Issue number9
DOIs
StatePublished - Mar 5 2008

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gemcitabine
Fluorouracil
Adenocarcinoma
Randomized Controlled Trials
Radiation
Drug Therapy
Survival
Radiotherapy
Confidence Intervals
Adjuvant Chemotherapy
Pancreatic Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

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Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma : A randomized controlled trial. / Regine, William F.; Winter, Kathryn A.; Abrams, Ross A.; Safran, Howard; Hoffman, John P.; Konski, Andre; Benson, Al B.; Macdonald, John S.; Kudrimoti, Mahesh R.; Fromm, Mitchel L.; Haddock, Michael; Schaefer, Paul; Willett, Christopher G.; Rich, Tyvin A.

In: JAMA - Journal of the American Medical Association, Vol. 299, No. 9, 05.03.2008, p. 1019-1026.

Research output: Contribution to journalArticle

Regine, WF, Winter, KA, Abrams, RA, Safran, H, Hoffman, JP, Konski, A, Benson, AB, Macdonald, JS, Kudrimoti, MR, Fromm, ML, Haddock, M, Schaefer, P, Willett, CG & Rich, TA 2008, 'Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: A randomized controlled trial', JAMA - Journal of the American Medical Association, vol. 299, no. 9, pp. 1019-1026. https://doi.org/10.1001/jama.299.9.1019
Regine, William F. ; Winter, Kathryn A. ; Abrams, Ross A. ; Safran, Howard ; Hoffman, John P. ; Konski, Andre ; Benson, Al B. ; Macdonald, John S. ; Kudrimoti, Mahesh R. ; Fromm, Mitchel L. ; Haddock, Michael ; Schaefer, Paul ; Willett, Christopher G. ; Rich, Tyvin A. / Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma : A randomized controlled trial. In: JAMA - Journal of the American Medical Association. 2008 ; Vol. 299, No. 9. pp. 1019-1026.
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title = "Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: A randomized controlled trial",
abstract = "Context: Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil. Objective: To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. Design, Setting, and Participants: Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. Intervention: Chemotherapy with either fluorouracil (continuous infusion of 250mg/m2 per day; n=230) or gemcitabine (30-minute infusion of 1000 mg/m2 once per week; n=221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m2 per day) was the same for all patients (50.4 Gy). Main Outcome Measures: Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. Results: A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n=388) had a median survival of 20.5 months and a 3-year survival of 31{\%} in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22{\%} in the fluorouracil group (hazard ratio, 0.82 [95{\%} confidence interval, 0.65-1.03]; P=.09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95{\%} confidence interval, 0.63-1.00]; P=.05). Grade 4 hematologic toxicity was 1{\%} in the fluorouracil group and 14{\%} in the gemcitabine group (P<.001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (>85{\%}). Conclusions: The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. Trial Registration: clinicaltrials.gov Identifier: NCT00003216.",
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T1 - Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma

T2 - A randomized controlled trial

AU - Regine, William F.

AU - Winter, Kathryn A.

AU - Abrams, Ross A.

AU - Safran, Howard

AU - Hoffman, John P.

AU - Konski, Andre

AU - Benson, Al B.

AU - Macdonald, John S.

AU - Kudrimoti, Mahesh R.

AU - Fromm, Mitchel L.

AU - Haddock, Michael

AU - Schaefer, Paul

AU - Willett, Christopher G.

AU - Rich, Tyvin A.

PY - 2008/3/5

Y1 - 2008/3/5

N2 - Context: Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil. Objective: To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. Design, Setting, and Participants: Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. Intervention: Chemotherapy with either fluorouracil (continuous infusion of 250mg/m2 per day; n=230) or gemcitabine (30-minute infusion of 1000 mg/m2 once per week; n=221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m2 per day) was the same for all patients (50.4 Gy). Main Outcome Measures: Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. Results: A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n=388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P=.09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P=.05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (P<.001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (>85%). Conclusions: The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. Trial Registration: clinicaltrials.gov Identifier: NCT00003216.

AB - Context: Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil. Objective: To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. Design, Setting, and Participants: Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. Intervention: Chemotherapy with either fluorouracil (continuous infusion of 250mg/m2 per day; n=230) or gemcitabine (30-minute infusion of 1000 mg/m2 once per week; n=221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m2 per day) was the same for all patients (50.4 Gy). Main Outcome Measures: Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. Results: A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n=388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P=.09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P=.05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (P<.001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (>85%). Conclusions: The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. Trial Registration: clinicaltrials.gov Identifier: NCT00003216.

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