Radiation Therapy Plus Chemotherapy Followed by Surgery in Treating Patients With Locally Advanced Cancer of the Rectum

Study Overview
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Brief Summary
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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 which regimen of radiation therapy plus chemotherapy is more effective for rectal cancer. PURPOSE: Randomized phase II trial to compare two regimens of radiation therapy plus chemotherapy followed by surgery in treating patients who have locally advanced cancer of the rectum.

Detailed Description
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OBJECTIVES: Compare the pathological complete response, acute and late normal tissue morbidity, patterns of failure, and complete resection rates in patients with locally advanced adenocarcinoma of the distal rectum treated with neoadjuvant chemoradiotherapy comprised of hyperfractionated radiotherapy and fluorouracil vs conventional radiotherapy, fluorouracil, and irinotecan, followed by radical resection. OUTLINE: This is a randomized study. Patients are stratified according to clinical stage (T3 vs T4). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive hyperfractionated radiotherapy (RT) twice daily, 5 days a week for 19 days. Patients receive fluorouracil IV continuously over 7 days a week concurrently with RT. Patients with clinical stage T3 or fixed T4 disease also receive a higher boost dose of RT to tumor. Arm II: Patients receive conventional RT once daily, 5 days a week for 25 days. Patients receive fluorouracil IV continuously over 5 days a week concurrently with RT. Patients receive irinotecan IV over 1 hour (immediately prior to RT dose) once weekly for 4 weeks. Patients with clinical stage T3 or fixed T4 disease also receive a lower boost dose of RT to tumor. Within 4-10 weeks after completion of chemoradiotherapy, patients on both arms undergo radical anterior resection or radical abdominal perineal resection with preferably a total mesorectal resection. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 100 patients (50 per arm) will be accrued for this study within 18 months.

Official Title
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Randomized Phase II Trial of Preoperative Combined Modality Chemoradiation for Distal Rectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the distal rectum Located 0-9 cm from the dentate line (3-12 cm from the anal verge) No extension of malignant disease into the anal canal Lesions may be mobile stage T3 by endorectal ultrasound OR fixed, defined as clinical stage T4, by palpation No evidence of distant metastases PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Zubrod 0-1 Life expectancy: Not specified Hematopoietic: WBC (white blood cell count) greater than 4,000/mm^3 Platelet count greater than 130,000/mm^3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal Alkaline phosphatase, SGOT (serum glutamic oxaloacetic transaminase), and LDH (lactate dehydrogenase) normal Renal: Creatinine normal Other: Not pregnant or nursing Fertile patients must use effective contraception No other invasive malignancy within the past 5 years except: Inactive nonmelanomatous skin cancer Carcinoma in situ of the cervix Synchronous colonic cancer if tumor is Tis or T1 and has been completely resected No other serious medical illnesses PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to pelvis Surgery: Not specified Other: No concurrent antiepileptic drugs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fluorouracil|nan|
|Drug: irinotecan hydrochloride|nan|
|Procedure: conventional surgery|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum