Radiation Therapy With or Without Chemotherapy Before Surgery in Treating Patients With Stage II or Stage III Rectal Cancer

OBJECTIVES:

• Compare the recurrence-free and overall survival of patients with resectable stage II or III adenocarcinoma of the rectum treated with neoadjuvant radiotherapy with or without concurrent chemotherapy comprising fluorouracil and leucovorin calcium followed by surgery and adjuvant fluorouracil and leucovorin calcium.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, gender, location of the tumor relative to the anal margin (0-5 cm vs > 5 cm), and tumor stage (T3 vs T4). Patients are randomized to 1 of 2 treatment arms.

• Neoadjuvant therapy: Patients are randomized to 1 of 2 neoadjuvant therapy arms.

• Arm I: Patients receive leucovorin calcium IV and fluorouracil IV over 15 minutes on days 1-5. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent radiotherapy 5 days a week for 5 weeks.
• Arm II: Patients undergo radiotherapy as in arm I.
• Surgery: In both arms, patients undergo surgical resection within 3-10 weeks after completing neoadjuvant therapy.
• Adjuvant therapy: Within 3-10 weeks after surgery, all patients receive adjuvant chemotherapy comprising leucovorin calcium IV and fluorouracil IV over 15 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for at least 5 years.

PROJECTED ACCRUAL: A total of 762 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the rectum meeting 1 of the following stage criteria:

• Stage T3, N0-2, M0 disease meeting 1 of the following criteria:

• Invasive disease in entire circumference (circular tumor)
• Tumor fixed laterally or posteriorly to pelvic structures
• Tumor adherent to the prostate and/or seminal vesicles
• Tumor infiltration into the vaginal-rectal septum
• Tumor classified as uT3 by rectal endoscopy
• Stage T4, N0-2, M0 disease meeting 1 of the following criteria:

• Clinical or radiologic evidence of pelvic organ extension (vagina, prostate, seminal vesicles, or bladder)
• Tumor extension to the anal canal or sphincter
• Tumor classified as uT4 by rectal endoscopy
• Tumor accessible by digital rectal exam
• Resectable disease
• No distant metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Creatinine < 1.36 mg/dL
• Granulocyte count > 2,000/mm^3
• Platelet count > 130,000/mm^3
• No progressive ischemic cardiomyopathy
• No acute or chronic obstruction unless treated with diversion colostomy
• No chronic inflammation of the ileum and/or colon
• No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, radiotherapy, or surgery for this cancer