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

Federation Francophone de Cancerologie Digestive

Status and phase: Completed; Phase 3

Conditions: Colorectal Cancer

Treatments: Drug: fluorouracil; Drug: leucovorin calcium; Procedure: conventional surgery; Radiation: radiation therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00296608

FFCD-9203

CDR0000466625

EU-20600

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy and chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether radiation therapy is more effective with or without chemotherapy when given before surgery for rectal cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy given together with fluorouracil and leucovorin to see how well they work compared to giving radiation therapy alone before surgery in treating patients with stage II or stage III rectal cancer.

Full description

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.

Enrollment: 762 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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762 participants in 2 patient groups

Radiotherapy

Active Comparator group

Description:

RT was delivered with photons from a linear accelerator with an energy level of 8MVor above.

Treatment:

Radiation: radiation therapy

Procedure: conventional surgery

Chemotherapy and radiotherapy

Experimental group

Description:

The first CT cycle was administered from days 1 to 5 of the RT treatment. LV 20 mg/m2/d was delivered intravenously immediately before administration of FU. FU 350 mg/m2/d was delivered during 20 minutes in 100 mL of saline infusion, 1 hour before RT. The second cycle was administered from days 29 to 33 of the RT treatment using the same schedule.

Treatment:

Radiation: radiation therapy

Procedure: conventional surgery

Drug: fluorouracil

Drug: leucovorin calcium