Document Detail


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.
MedLine Citation:
PMID:  22782416     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 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; χ2 = 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 χ2 = 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.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201.
Authors:
John P Neoptolemos; Malcolm J Moore; Trevor F Cox; Juan W Valle; Daniel H Palmer; Alexander C McDonald; Ross Carter; Niall C Tebbutt; Christos Dervenis; David Smith; Bengt Glimelius; Richard M Charnley; François Lacaine; Andrew G Scarfe; Mark R Middleton; Alan Anthoney; Paula Ghaneh; Christopher M Halloran; Markus M Lerch; Attila Oláh; Charlotte L Rawcliffe; Caroline S Verbeke; Fiona Campbell; Markus W Büchler;
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Publication Detail:
Type:  Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA     Volume:  308     ISSN:  1538-3598     ISO Abbreviation:  JAMA     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-11     Completed Date:  2012-07-12     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  147-56     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00058201
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / drug therapy*,  surgery
Aged
Ampulla of Vater
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Chemotherapy, Adjuvant
Common Bile Duct Neoplasms / drug therapy*,  surgery
Deoxycytidine / administration & dosage,  analogs & derivatives
Female
Fluorouracil / administration & dosage
Humans
Leucovorin / administration & dosage
Male
Middle Aged
Prognosis
Survival Analysis
Watchful Waiting*
Grant Support
ID/Acronym/Agency:
9855//Cancer Research UK; //Cancer Research UK
Chemical
Reg. No./Substance:
0W860991D6/Deoxycytidine; B76N6SBZ8R/gemcitabine; Q573I9DVLP/Leucovorin; U3P01618RT/Fluorouracil
Investigator
Investigator/Affiliation:
R C G Russell / ; R P Ahern / ; P Clarke / ; E Abdi / ; S Ackland / ; M Brown / ; W I Burns / ; I Byard / ; P Cooray / ; M Doreen / ; R Eek / ; D Grimes / ; A Haydon / ; P Kho / ; F Kirstan / ; G Marx / ; E Moylan / ; F Parnis / ; J Shapiro / ; N Spry / ; B Stein / ; N Tebbutt / ; C Underhill / ; D Wyld / ; D Yip / ; M Bacon / ; E Bergeron / ; S Berry / ; C Butts / ; E Chen / ; B Colwell / ; C Cripps / ; M Doreen / ; R Feld / ; A Fields / ; D Jonker / ; I Kerr / ; J Knox / ; Y Ko / ; S Koski / ; M Moore / ; C O'Callaghan / ; A Oza / ; D Rayson / ; B Samson / ; M Sanatani / ; A Scarfe / ; S Singh / ; L Wood / ; M Ryska / ; R Strnad / ; I Nordback / ; T Salminen / ; J Sand / ; A Champault / ; F Lacaine / ; M Hebbar / ; C Mariette / ; J M Regimbeau / ; D Rio / ; M S Sbai-Idriasy / ; J Bachman / ; M W Buchler / ; M Diener / ; J Veit / ; M Wente / ; J Werner / ; A Chromik / ; I Esposito / ; A Frilling / ; C D Heidecke / ; P Herzog / ; D K Hossfeld / ; J R Izbicki / ; P Schafhausen / ; J Stohlmacher / ; M M Lerch / ; J Mayerle / ; C Nitsche / ; F Lordick / ; K Schoppmeyer / ; C Avgerinos / ; D Kelgiorgi / ; C Dervenis / ; E Chatzitheoklitos / ; A Katsourakis / ; D Kelemen / ; A Olah / ; A Pap / ; L Grogan / ; K O'Byrne / ; C Bassi / ; G Butterini / ; S Pedrazzoli / ; D Gibbs / ; S Connor / ; B Robinson / ; W Polkowski / ; M Milicevic / ; L Petronijevic / ; D Radenkovic / ; A Almerud / ; R Segersvärd / ; T Foukakis / ; P Lind / ; J Permert / ; E Rossman / ; A Andren-Sandberg / ; A Berglund / ; B Glimelius / ; B M Karlsson / ; P Nygren / ; C Bratthall / ; A Thune / ; F Adab / ; D J Adamson / ; A Anthoney / ; C Archer / ; C Askill / ; C A Baughan / ; S Bramhall / ; D Spooner / ; D D Stocken / ; C Johnson / ; P Johnson / ; J Bridgewater / ; R Carter / ; F Campbell / ; R Charnley / ; I Chau / ; M J Churn / ; P I Clark / ; P Corrie / ; F Coxon / ; T Crosby / ; F Daniel / ; B R Davidson / ; F Lofts / ; T Plunkett / ; D Propper / ; P Ross / ; T Meyer / ; J Dent / ; E J Dickson / ; M Eatock / ; T R J Evans / ; S Falk / ; D Ferry / ; D Furniss / ; D Fyfe / ; S Gollins / ; P Harper / ; M N Hartley / ; A B Hassan / ; R Hawkins / ; B Haylock / ; M Highley / ; M Hill / ; C W Imrie / ; T Iveson / ; A Jamil / ; A Kingsnorth / ; R Kulkarni / ; J A Ledermann / ; P C Leonard / ; S Madhusudan / ; U Mallick / ; A Maraveyas / ; E Marshall / ; T S Maughan / ; K Mcadam / ; A Mcdonald / ; C J McKay / ; M Middleton / ; R Midgley / ; G Middleton / ; S Mukherjee / ; P Mulvenna / ; M Napier / ; B T Orr / ; R Osborne / ; M J Ostrowski / ; S Pascoe / ; M Seymour / ; A Shaukat / ; D Smith / ; S Sothi / ; W Steward / ; R Sutton / ; S Tahir / ; A R Todd / ; E Toy / ; G Ullenhag / ; J Valle / ; C S Verbeke / ; N Wadd / ; J Wadsley / ; L Wall / ; N Warner / ; H Wasan / ; J Waters / ; C Wilson /
Comments/Corrections
Comment In:
JAMA. 2012 Nov 14;308(18):1855; author reply 1855-6   [PMID:  23149995 ]
Erratum In:
JAMA. 2012 Nov 14;308(18):1861

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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