Effect of Adjuvant Chemotherapy With Fluorouracil Plus Folinic Acid or Gemcitabine vs Observation on Survival in Patients With Resected Periampullary Adenocarcinoma The ESPAC-3 Periampullary Cancer Randomized Trial

被引:451
|
作者
Neoptolemos, John P. [1 ]
Moore, Malcolm J. [2 ]
Cox, Trevor F. [1 ]
Valle, Juan W. [3 ]
Palmer, Daniel H. [4 ]
McDonald, Alexander C. [5 ]
Carter, Ross [6 ]
Tebbutt, Niall C. [7 ]
Dervenis, Christos [8 ]
Smith, David [9 ]
Glimelius, Bengt [10 ]
Charnley, Richard M. [11 ]
Lacaine, Francois [12 ]
Scarfe, Andrew G. [13 ]
Middleton, Mark R. [14 ]
Anthoney, Alan [15 ]
Ghaneh, Paula [1 ]
Halloran, Christopher M. [1 ]
Lerch, Markus M. [16 ]
Olah, Attila [17 ]
Rawcliffe, Charlotte L. [1 ]
Verbeke, Caroline S. [18 ]
Campbell, Fiona [1 ]
Buechler, Markus W. [19 ]
机构
[1] Univ Liverpool, Canc Res United Kingdom Ctr, Liverpool Canc Trials Unit, Inst Translat Med, Liverpool L69 3GA, Merseyside, England
[2] Princess Margaret Hosp, Dept Med, Div Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada
[3] Univ Manchester, Sch Canc & Enabling Sci, Christie NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester M13 9PL, Lancs, England
[4] Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp, Sch Canc Sci, Canc Res UK Inst Canc Studies, Birmingham, W Midlands, England
[5] Beatson W Scotland Canc Ctr, Glasgow, Lanark, Scotland
[6] Glasgow Royal Infirm, Dept Surg, Glasgow G4 0SF, Lanark, Scotland
[7] Austin Hlth, Ludwig Oncol Unit, Melbourne, Vic, Australia
[8] Agia Olga Hosp, Dept Surg, Athens, Greece
[9] Clatterbridge Ctr Oncol, Bebington, Merseyside, England
[10] Uppsala Univ, Akad Sjukhuset, Dept Oncol, Uppsala, Sweden
[11] Freeman Rd Hosp, Dept Surg, Newcastle Upon Tyne, Tyne & Wear, England
[12] Hop Tenon, Serv Chirurg Digest & Viscerale, F-75970 Paris, France
[13] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada
[14] Oxford Univ Hosp NHS Trust, Churchill Hosp, Dept Oncol, Oxford, England
[15] St James Univ Hosp, Dept Oncol, Leeds, W Yorkshire, England
[16] Univ Greifswald, Dept Med, Greifswald, Germany
[17] Petz Aladar Hosp, Dept Surg, Gyor, Hungary
[18] Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden
[19] Heidelberg Univ, Dept Surg, D-6900 Heidelberg, Germany
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2012年 / 308卷 / 02期
基金
英国医学研究理事会;
关键词
PANCREATIC-CANCER; PROGNOSTIC-FACTORS; AMPULLARY; PANCREATICODUODENECTOMY; CHEMORADIOTHERAPY; DIFFERENTIATION;
D O I
10.1001/jama.2012.7352
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas. Objective To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection. Design, Setting, and Patients The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers. Interventions One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m(2) of folinic acid via intravenous bolus injection followed by 425 mg/m(2) of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m(2) of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months. Main Outcome Measures The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life. Results Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; chi(2)=1.33; P=.25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald chi(2)=4.53, P=.03). Conclusions Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy
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页码:147 / 156
页数:10
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