RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether giving radiation therapy before surgery is more effective than giving chemotherapy plus radiation therapy after surgery in treating patients with rectal cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy given before surgery to see how well it works compared to chemotherapy and radiation therapy given after surgery in treating patients with rectal cancer that can be surgically removed.

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

Further Study Details: 

OBJECTIVES:

• Compare local recurrence free rates and quality of life in patients with operable rectal cancer receiving preoperative radiotherapy versus patients receiving selective postoperative chemoradiotherapy.
• Determine local recurrence free survival, overall survival, time to appearance of distant metastases, disease free survival and morbidity in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by a number of factors including surgeon.

Patients are randomized to receive preoperative radiotherapy (arm I) or postoperative chemoradiotherapy (arm II).

• Arm I: Patients receive radiotherapy in 5 fractions over 1 week prior to surgery. Patients undergo surgery within 7 days of the last fraction of radiotherapy.
• Arm II: Patients receive chemoradiotherapy 4-12 weeks after surgery (if circumferential resection margins are histologically involved by tumor). Radiotherapy is administered in 25 fractions over 5 weeks (5 days per week). During radiotherapy, patients either receive fluorouracil (5-FU) continuous infusion, 5-FU bolus IV and leucovorin calcium IV weekly, or a 5-day bolus schedule of 5-FU and leucovorin calcium. Patients may then receive adjuvant chemotherapy as per local policy.

Quality of life assessments are made every 3 months for 1 year and then every 6 months for the next 2 years.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 1800 patients will be accrued into this study.

Ages Eligible for Study:  up to  75 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the rectum (defined as lower edge of tumor within 15 cm of anal verge)
• Tumor considered potentially operable
• No evidence of metastases indicated by liver ultrasound or CT scan; chest x-ray; or renal, liver, and bone profiles

PATIENT CHARACTERISTICS: Age:

• 75 and under

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No uncontrolled heart failure or angina

Other:

• No other concurrent uncontrolled medical illness (e.g., infection)
• No other prior or concurrent malignancy likely to interfere with the protocol treatments or comparisons

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Canada, Quebec
      Hopital Charles Lemoyne, Greenfield Park,  Quebec,  J4V 2H1,  Canada; Recruiting
United Kingdom, Scotland
      Ninewells Hospital and Medical School, Dundee,  Scotland,  DD1 9SY,  United Kingdom; Recruiting

Study chairs or principal investigators

R. Steele,  Study Chair,  Ninewells Hospital and Medical School   
Jean Couture, MD,  Study Chair,  Hopital Charles Lemoyne   

Study ID Numbers:  CDR0000066442; MRC-CR07; EU-98008; CAN-NCIC-C016; ISRCTN28785842; NCT00003422
Record last reviewed:  September 2003
Last Updated:  February 9, 2005
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003422
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08