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Radiation Therapy, Surgery, and Chemotherapy in Treating Patients With Rectal Cancer That Can Be Surgically Removed

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00002523
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : September 2, 2016
Information provided by (Responsible Party):

Study Description
Brief Summary:

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 or disease Intervention/treatment Phase
Colorectal Cancer Drug: fluorouracil Drug: leucovorin calcium Procedure: conventional surgery Radiation: radiation therapy Phase 3

Detailed Description:


  • 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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1011 participants
Allocation: Randomized
Primary Purpose: Treatment
Study Start Date : April 1993
Primary Completion Date : March 2003
Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 80 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 80 and under

Performance status:

  • WHO 0-1

Life expectancy:

  • Not specified


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


  • Not specified


  • Creatinine less than 1.36 mg/dL


  • No angina pectoris


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


Biologic therapy

  • No prior biologic therapy for adenocarcinoma of the rectum


  • No prior chemotherapy for adenocarcinoma of the rectum

Endocrine therapy

  • No prior endocrine therapy for adenocarcinoma of the rectum


  • No prior radiotherapy for adenocarcinoma of the rectum


  • No prior surgery for adenocarcinoma of the rectum
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002523

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

Bosset J, Calais G, Mineur L, et al.: Preoperative radiotherapy in rectal cancer: role and place of fluorouracil-based chemotherapy. Final results of the EORTC 22921 phase III trial. [Abstract] American Society of Clinical Oncology 2005 Gastrointestinal Cancers Symposium, 27-29 January 2005, Miami, Florida. A-255, 2005.
Bosset JF, Calais G, Mineur L, et al.: Preoperative radiation (Preop RT) in rectal cancer: effect and timing of additional chemotherapy (CT) 5-year results of the EORTC 22921 trial. [Abstract] J Clin Oncol 23 (Suppl 16): A-3505, 247s, 2005.
Bosset JF, Calais G, Mineur L, et al.: Does the addition of chemotherapy (CT) to preoperative radiotherapy (preopRT) increase the pathological response in patients with resected rectal cancer: report of the 22921 EORTC phase III trial. [Abstract] J Clin Oncol 22 (Suppl 14): A-3504, 246, 2004.
Bosset JF, Calais G, Daban A, et al.: Does the addition of chemotherapy to preoperative radiation increase acute toxicity in patients with rectal cancer: report of 22921 EORTC phase III trial . [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1179, 2003.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00002523     History of Changes
Other Study ID Numbers: EORTC-22921
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: September 2, 2016
Last Verified: September 2016

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage II rectal cancer
stage III rectal cancer
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Rectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protective Agents