RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells.
Intensity-modulated radiation therapy (radiation directed at the tumor more precisely than
in standard radiation therapy) with incorporated boost (an increase in the amount of
radiation given during treatment) may cause less damage to normal tissue. Drugs used in
chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing
so they stop growing or die. Giving radiation therapy together with chemotherapy before
surgery may shrink the tumor so it can be removed.
PURPOSE: This phase I trial is studying the side effects and best dose of neoadjuvant
intensity-modulated radiation therapy with incorporated boost when given together with
capecitabine in treating patients with locally advanced rectal cancer.
- Determine the maximum tolerated dose of neoadjuvant boost intensity-modulated
radiotherapy when combined with capecitabine before surgery in patients with locally
advanced rectal cancer.
- 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.
- 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
- 18 and over
- ECOG 0-1
- More than 3 months
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- No known, uncontrolled coagulopathy
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- SGOT and SGPT ≤ 1.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- Creatinine ≤ 1.5 times normal
- Creatinine clearance > 50 mL/min
- 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
- No active inflammatory bowel disease
- No lack of physical integrity of the upper gastrointestinal tract
- No malabsorption syndrome
- 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
PRIOR CONCURRENT THERAPY:
- No prior immunotherapy for rectal cancer
- No prior chemotherapy for rectal cancer
- Not specified
- No prior radiotherapy for rectal cancer
- No prior pelvic radiotherapy
- More than 4 weeks since prior major surgery and recovered
- No prior surgery for rectal cancer
- More than 4 weeks since prior participation in another investigational drug study
- No concurrent celecoxib