RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so it can be removed during surgery. It is not yet known if surgery is more effective with or without radiation therapy and chemotherapy in treating esophageal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without radiation therapy and chemotherapy in treating patients who have esophageal cancer.

Condition	Treatment or Intervention	Phase
Adenocarcinoma of the Esophagus squamous cell carcinoma of the esophagus stage I esophageal cancer stage II esophageal cancer	Drug: cisplatin  Drug: fluorouracil  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: neoadjuvant therapy  Procedure: radiation therapy  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the overall survival of patients with resectable thoracic esophageal cancer treated with neoadjuvant radio-chemotherapy and surgery versus surgery alone.
• Compare the disease-free survival of patients treated with these regimens.
• Compare the surgical mortality and morbidity of patients treated with these regimens.
• Compare the resectability of patients treated with these regimens.
• Determine the validation of new prognostic factors for survival of these patients and/or the efficacy of this neoadjuvant treatment.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to histology (epidermoid carcinoma vs adenocarcinoma vs undifferentiated carcinoma), stage (I vs IIA vs IIB), tumor location (above the carina vs below the carina), and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy daily 5 days a week for 5 weeks. Patients receive fluorouracil IV continuously on days 1-4 and 29-32 and cisplatin IV on days 1 or 2 and 29 or 30 (or a lower dose on days 1-5 and 29-33). Within 4-8 weeks after completion of radio-chemotherapy, patients undergo surgical resection.
• Arm II: Patients undergo surgical resection. Patients are followed every 4 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 380 patients (190 per treatment arm) will be accrued for this study within 3 years.

Ages Eligible for Study:  up to  74 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of stage I or II thoracic esophageal cancer
• Tumor no greater than 3 cm with no invasion of mediastinal structures with or without extension to the lymph nodes (T1-2, N0-1, M0) OR
• Tumor greater than 3 cm with no invasion of mediastinal structures and no adenopathy greater than 1 cm (T3, N0, M0)
• Epidermoid carcinoma or adenocarcinoma
• Previously untreated
• Deemed resectable with curative intent
• No carcinoma in situ
• No small cell anaplastic carcinoma (i.e., chromogranin negative)
• No small cell neuroendocrine carcinoma (i.e., chromogranin positive)
• No multifocal esophageal carcinoma (i.e., 2 or more distinct lesions 5 or more cm apart)
• No involvement of the pharyngoesophageal junction and the first 4 cm of the esophagus (i.e., where the proximal edge of the tumor is less than 19 cm from the dental arch)
• No evidence of extension to the tracheobronchial tree at endoscopy, ultrasound, or CT scan (simple compression allowed)
• No signs of mediastinal involvement on CT scan
• No palpable subclavicular lymph nodes or involvement after cytology needle aspiration
• No lymph nodes from the origin of the celiac greater than 1 cm on CT scan
• Perigastric lymph nodes far from the celiac trunk and deemed resectable allowed unless tumor is more than 30 mm on CT scan

PATIENT CHARACTERISTICS: Age

• Under 75

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• SGOT/SGPT ratio no greater than 1
• Albumin at least 35 g/L
• Total protein greater than 80%
• No liver cirrhosis with previous failure
• No ascites
• No jaundice
• No rupture of varicose esophageal veins
• No presence of varicose esophageal veins

Renal

• Creatinine no greater than 1.25 times normal

Cardiovascular

• Arterial O_2 greater than 60 mm Hg
• Arterial CO_2 no greater than 45 mm Hg
• No myocardial infarction within the past 6 months
• No progressive coronary artery disease grade 2 or greater
• No recent left ventricular failure
• No arterial disease stage II-IV

Pulmonary

• FEV_1 greater than 1 L/sec

Other

• Able to receive either study treatment
• No recurrent paralysis
• No weight loss greater than 10% from baseline
• No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• Not pregnant
• Fertile patients must use effective contraception during and for 3 months after completion of chemotherapy

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Belgium
      CHR - Clinique Saint Joseph - Hopital de Warqueguies, Mons,  B-7000,  Belgium
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
      Universiteit Gent, Ghent,  B-9000,  Belgium
France
      Evreux,  27000,  France
      Assistance Publique Hopitaux de Marseille Hopitaux Sud, Marseille,  13274,  France
      C.H. Bourg En Bresse, Bourg-en-Bresse,  01012,  France
      C.H. Senlis, Senlis,  60309,  France
      Centre d'Oncologie Saint-Yves, Vannes,  56001,  France
      Centre Eugene Marquis, Rennes,  35042,  France
      Centre Gray, Maubeuge,  59600,  France
      Centre Hospitalier D'Agen, St. Esprit,  47000,  France
      Centre Hospitalier de Bourgoin - Jallieu, Bourgoin-Jallieu,  38300,  France
      Centre Hospitalier De Dunkerque - CHD, Dunkerque,  59240,  France
      Centre Hospitalier de Lagny, Compiegne,  60321,  France
      Centre Hospitalier de Meaux, Meaux,  77104,  France
      Centre Hospitalier De Pontivy, Pontivy,  56300,  France
      Centre Hospitalier de Valenciennes, Valenciennes,  59300,  France
      Centre Hospitalier Departemental, La Roche-sur-Yon,  F-85025,  France
      Centre Hospitalier Docteur Duchenne, Boulogne-sur-Mer,  62200,  France
      Centre Hospitalier General De Saint-Malo, Saint-Malo,  35400,  France
      Centre Hospitalier General, Brive,  19101,  France
      Centre Hospitalier Intercommunal de Poissy, Saint-Germain-en-Laye,  78104,  France
      Centre Hospitalier Lyon Sud, Pierre-Benite,  69495,  France
      Centre Hospitalier Regional et Universitaire d'Angers, Angers,  49033,  France
      Centre Hospitalier Regional et Universitaire de Lille, Lille,  59037,  France
      Centre Hospitalier Universitaire de Dijon, Dijon,  21034,  France
      Centre Hospitalier Universitaire, Reims,  51092,  France
      Centre Hospitalier, Mulhouse,  68070,  France
      Centre Jean Bernard, Le Mans,  72000,  France
      Centre Joliot Curie Des Docteurs Jean-Christophe Chardon Jacques Hernandez Et Laurent Gasnault, Saint-Martin-Boulogne,  62280,  France
      Centre Oscar Lambret, Lille,  59020,  France
      Centre Paul Papin, Angers,  49036,  France
      Centre Paul Strauss, Strasbourg,  67065,  France
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France
      Centre Rene Huguenin, Saint Cloud,  92210,  France
      CH Meulan, Meulan,  78250,  France
      CHR Clermont Ferrand, Hotel dieu, Clermont-Ferrand,  63003,  France
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France
      CHR D'Orleans - Hopital de la Source, Orleans,  45067,  France
      CHR Hotel Dieu, Nantes,  44093,  France
      CHU Ambroise Pare, Boulogne-Billancourt,  F-92104,  France
      CHU Brest - Hopital De La Cavale Blanche, Brest,  29200,  France
      CHU de Caen, Caen,  14033,  France
      CHU de la Timone, Marseille,  13385,  France
      CHU de Nancy - Hopitaux de Brabois, Vandoeuvre-les-Nancy,  54511,  France
      CHU de Tours, Tours,  37044,  France
      Clinique Sainte Clotilde, Sainte Clotilde,  97492,  France
      Clinique Sainte Marie, Chalon-sur-Saone,  71100,  France
      Hopital Andre Mignot, Le Chesnay,  78157,  France
      Hopital Beaujon, Clichy,  92118,  France
      Hopital de la Croix Rousse, Lyon,  69317,  France
      Hopital de l'Archet, Nice,  F-06202,  France
      Hopital Europeen Georges Pompidou, Paris,  75015,  France
      Hopital Jean Bernard, Poitiers,  86021,  France
      Hopital Louis Pasteur, Colmar,  68024,  France
      Hopital Notre-Dame de Bon Secours, Metz,  57038,  France
      Hopital Robert Boulin, Libourne,  33500,  France
      Hopital Saint Antoine, Paris,  75012,  France
      Hopital Universitaire Hautepierre, Strasbourg,  67098,  France
      Hopitaux Universitaire de Strasbourg, Strasbourg,  67091,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
      Institut J. Paoli and I. Calmettes, Marseille,  13273,  France
      Institut Jean Godinot, Reims,  51056,  France
      Arras,  62000,  France
      Nouvelle Clinique Generale, Valence,  26000,  France
      Polyclinique Du Bois, Lille,  59000,  France
Germany
      Klinikum der Albert - Ludwigs - Universitaet Freiburg, Freiburg,  D-79106,  Germany
      Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch, Berlin,  D-13122,  Germany
      Universitaet Erlangen, Erlangen,  D-91054,  Germany
      Universitaets-Krankenhaus Eppendorf, Hamburg,  D-20246,  Germany
Netherlands
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands

Study chairs or principal investigators

J. P. Triboulet,  Study Chair,  Centre Hospitalier Regional et Universitaire de Lille   
Gerard Ganem, MD,  Study Chair,  Centre Jean Bernard   
Jean-Francois Bosset, MD,  CHR de Besancon - Hopital Jean Minjoz   
Thierry Conroy, MD,  Centre Alexis Vautrin   
Jean Francois Seitz, MD,  Study Chair,  Institut J. Paoli and I. Calmettes   
Francoise Mornex, MD, PhD,  Study Chair,  Centre Hospitalier Lyon Sud   

Study ID Numbers:  CDR0000257600; FFCD-9901; EORTC-22001; EORTC-40001; FRE-FNCLCC-FFCD-9901; FRE-GERCOR-FFCD-9901; SFRO-FFCD-9901; EU-20215; NCT00047112
Record last reviewed:  March 2005
Last Updated:  March 10, 2005
Record first received:  October 3, 2002
ClinicalTrials.gov Identifier:  NCT00047112
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08