RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, giving the drugs in different ways, and combining radiation therapy and surgery with chemotherapy may kill more tumor cells.

PURPOSE: Randomized phase III trial to compare radiation therapy alone before surgery with radiation therapy plus fluorouracil and leucovorin before surgery, with and without fluorouracil and leucovorin after surgery in patients with rectal cancer that can be surgically removed.

Condition	Treatment or Intervention	Phase
stage II rectal cancer stage III rectal cancer adenocarcinoma of the rectum	Drug: fluorouracil  Drug: leucovorin calcium  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: drug modulation  Procedure: radiation therapy  Procedure: radiosensitization  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the disease-free and overall survival in patients with resectable adenocarcinoma of the rectum treated with preoperative radiotherapy with or without preoperative fluorouracil (5-FU) combined with leucovorin calcium (CF) and/or postoperative 5-FU/CF.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, sex, tumor location (0-5 vs 6-10 vs 11-15 cm from anal margin), and stage (T3 vs T4). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients undergo involved-field radiotherapy 5 days a week for 5 weeks followed 3-10 weeks later by abdominoperineal resection or anal-sparing resection according to local practice in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo radiotherapy as in arm I beginning on day 1 and leucovorin calcium (CF) IV followed by fluorouracil (5-FU) IV (1 hour before radiotherapy) on days 1-5 and 29-33, followed 3-10 weeks later by resection as in arm I in the absence of disease progression or unacceptable toxicity.
• Arm III: Patients undergo radiotherapy followed 3-10 weeks later by resection as in arm I. Within 3-10 weeks after resection, patients receive CF followed by 5-FU on days 1-5. Chemotherapy continues every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
• Arm IV: Patients undergo preoperative radiotherapy with concurrent chemotherapy followed by resection as in arm II and postoperative chemotherapy as in arm III. Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 992 patients will be accrued for this study within 4 years.

Ages Eligible for Study:  up to  80 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed resectable adenocarcinoma of the rectum
• Any grade
• Tumor macroscopically within 15 cm of anal margin on rigid rectoscopy
• Tumor tethered or partially fixed on digital rectal exam and/or T3-4 on rectal ultrasound
• No acute or subacute bowel obstruction without colostomy diversion
• No chronic inflammatory disease of the ileum and/or colon
• No primary adenocarcinoma of the anal canal
• No distant metastasis

PATIENT CHARACTERISTICS: Age:

• 80 and under

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count greater than 2,000/mm^3
• Platelet count greater than 130,000/mm^3

Hepatic:

• Not specified

Renal:

• Creatinine less than 1.36 mg/dL

Cardiovascular:

• No angina pectoris

Other:

• No other prior malignancy except basal cell skin cancer or carcinoma in situ of the uterine cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior biologic therapy for adenocarcinoma of the rectum

Chemotherapy

• No prior chemotherapy for adenocarcinoma of the rectum

Endocrine therapy

• No prior endocrine therapy for adenocarcinoma of the rectum

Radiotherapy

• No prior radiotherapy for adenocarcinoma of the rectum

Surgery

• No prior surgery for adenocarcinoma of the rectum

Belgium
      Centre Hospitalier Universitaire de Tivoli, La Louviere,  7100,  Belgium
      Clinique Sainte Elisabeth, Namur,  5000,  Belgium
      Hopital Civil de Charleroi, Charleroi,  6000,  Belgium
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
France
      C.H.U. de Brest, Brest,  29200,  France
      Centre de Lutte Contre le Cancer, Georges-Francois Leclerc, Dijon,  21079,  France
      Centre Hospital Regional Universitaire de Limoges, Limoges,  87042,  France
      Centre Hospitalier General, Belfort,  90000,  France
      Centre Hospitalier Universitaire Bretonneau de Tours, Tours,  37044,  France
      Centre Hospitalier Universitaire Henri Mondor, Creteil,  94010,  France
      Centre Oscar Lambret, Lille,  59020,  France
      Centre Paul Papin, Angers,  49036,  France
      Centre Paul Strauss, Strasbourg,  67085,  France
      Centre Saint-Yves, Vannes,  56001,  France
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France
      CHR de Grenoble - La Tronche, Grenoble,  38043,  France
      Clinique De Valdegour, Nimes,  30900,  France
      Clinique Sainte Clotilde, Sainte Clotilde,  97492,  France
      CRLCC Nantes - Atlantique, Nantes-Saint Herblain,  44805,  France
      Hopital Jean Bernard, Poitiers,  86021,  France
      Institut Sainte Catherine, Avignon,  84082,  France
      Service Cancerologie Polyclinique Clairval, Marseille,  13009,  France
Germany
      Krankenhaus des Kreises Hameln-Pyrmont, Hameln,  31785,  Germany
Israel
      Rambam Medical Center, Haifa,  31096,  Israel
Netherlands
      Dr. Bernard Verbeeten Instituut, Tilburg,  5042 SB,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands
Poland
      Medical University of Gdansk, Gdansk,  80-211,  Poland
Spain
      Hospital General Gregorio Maranon, Madrid,  28007,  Spain
      Hospital General Universitari Vall d'Hebron, Barcelona,  08035,  Spain
      Institut Catala d'Oncologia - Hospital Duran i Reynals, Barcelona,  08907,  Spain
Switzerland
      Kantonsspital Basel, Basel,  CH-4000,  Switzerland
      UniversitaetsSpital, Zurich,  CH-8091,  Switzerland
Turkey
      Dokuz Eylul University School of Medicine, Izmir,  35340,  Turkey
Yugoslavia
      Institute of Oncology and Radiology of Serbia, BELGRADE,  11000,  Yugoslavia

Study chairs or principal investigators

Jean Francois Bosset, MD,  Study Chair,  CHR de Besancon - Hopital Jean Minjoz   

Study ID Numbers:  CDR0000078308; EORTC-22921
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002523
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08