Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy in Treating Patients Who Are Undergoing Surgical Resection for Locally Advanced Rectal Cancer

Inclusion Criteria

• Adenocarcinoma of the rectum originating at or below 12 cm from the anal verge without evidence of distant metastases
• Patient must be 18 years of age or greater.
• Potentially resectable en bloc based upon surgeon evaluation
• Clinical stages T3 or T4, based upon endorectal ultrasound, or physical examination (only acceptable for T4 lesions).
• Absolute neutrophil count of > 1500 per microliter and platelet count > 100,000 per microliter; aspartate aminotransferase (AST) and alkaline phosphatase 50 ml/min using Cockcroft-Gault formula:
• CrCl male = (140 - age) x (wt. in kg) / (Serum Cr) x 72
• CrCl female = 0.85 x (CrCl male)
• Zubrod performance status 0-2
• No history of other malignancies within 5 years, except non-melanoma skin cancer, in situ carcinoma of the cervix, or ductal carcinoma in situ of the breast. Previous invasive cancer permitted if disease free at least 5 years.
• Signed study-specific informed consent prior to randomization

Exclusion Criteria

• Any evidence of distant metastasis
• Synchronous primary colon carcinomas, except T1 lesions (full colonoscopy not required for enrollment)
• Extension of malignant disease to the anal canal
• Prior radiation therapy to the pelvis
• Prior chemotherapy for malignancies
• Pregnancy or lactation, (exclusion due to potential adverse effects of therapy). Women of childbearing potential with either a positive or no pregnancy test (serum or urine) at baseline. Women/men of childbearing potential not using a reliable and appropriate contraceptive method. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered to be of non-childbearing potential.) Patients will agree to continue contraception for 30 days from the date of the last study drug administration.
• Serious, uncontrolled, concurrent infection(s).
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
• Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months.
• Evidence of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
• Other serious uncontrolled medical conditions that the investigator feels might compromise study participation.
• Major surgery within 4 weeks of the study treatment.
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
• Known, existing uncontrolled coagulopathy.
• No concurrent cimetidine allowed.