Intensity-Modulated Radiation Therapy With Incorporated Boost and Capecitabine Before Surgery in Treating Patients With Locally Advanced Rectal Cancer

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of neoadjuvant boost intensity-modulated radiotherapy when combined with capecitabine before surgery in patients with locally advanced rectal cancer.

Secondary

• Determine the pathologic tumor response in patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of boost intensity-modulated radiotherapy (IMRT).

Patients undergo neoadjuvant IMRT with incorporated boost once daily 5 days a week for 5 weeks. Beginning on the first day of radiotherapy, patients receive oral capecitabine twice daily 7 days a week for 5 weeks. Patients undergo surgical resection 4-8 weeks after completion of chemoradiotherapy.

Cohorts of 3-6 patients undergo escalating doses of boost IMRT until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.

Quality of life is assessed at baseline, at week 5 of chemoradiotherapy, before surgery, and then at 1, 3, and 12 months after surgery.

Patients are followed at 1, 3, and 12 months after surgery.

PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary adenocarcinoma of the rectum

• Distal border of the tumor within 12 cm of the anal verge by proctoscopic exam
• Clinical stage T3-4, N1-2 (stage II or III) disease by 2 of the following tests:

• Physical exam
• Transrectal ultrasound
• Pelvic CT scan
• Pelvic MRI
• No clinical evidence of metastatic disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No known, uncontrolled coagulopathy

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• SGOT and SGPT ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 times normal
• Creatinine clearance > 50 mL/min

Cardiovascular

• No clinically significant cardiac disease
• No congestive heart failure
• No symptomatic coronary artery disease
• No poorly controlled cardiac arrhythmias
• No myocardial infarction within the past year

Gastrointestinal

• No active inflammatory bowel disease
• No lack of physical integrity of the upper gastrointestinal tract
• No malabsorption syndrome

Other

• No other prior or concurrent malignancy except inactive, non-invasive carcinoma of the cervix or non-melanoma skin cancer
• No concurrent serious, uncontrolled infection(s)
• No prior unanticipated severe reaction to fluoropyrimidine therapy
• No known sensitivity to fluorouracil
• No prior uncontrolled seizures
• No CNS disorders that would preclude study participation
• No other medical or psychiatric condition that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy for rectal cancer

Chemotherapy

• No prior chemotherapy for rectal cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for rectal cancer
• No prior pelvic radiotherapy

Surgery

• More than 4 weeks since prior major surgery and recovered
• No prior surgery for rectal cancer

Other

• More than 4 weeks since prior participation in another investigational drug study
• No concurrent celecoxib