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

FOUR ARMS PHASE III CLINICAL TRIAL FOR T3-T4 RESECTABLE RECTAL CANCER COMPARING PRE-OPERATIVE PELVIC IRRADIATION TO PRE-OPERATIVE IRRADIATION COMBINED WITH FLUOROURACIL AND LEUCOVORIN WITH OR WITHOUT POST-OPERATIVE ADJUVANT CHEMOTHERAPY

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.

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.

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