oxaliplatin, fluorouracil, and external-beam radiation therapy followed by surgery in treating patients with locally advanced cancer of the rectum

Conditions: Adenocarcinoma of the Rectum; Stage II Rectal Cancer; Stage III Rectal Cancer

Summary: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. radiation therapy uses high-energy x-rays to damage tumor cells. combining chemotherapy, radiation therapy, and surgery may be a more effective treatment for cancer of the rectum. phase ii trial to study the effectiveness of combining oxaliplatin, fluorouracil, and external-beam radiation therapy followed by surgery in treating patients who have locally advanced cancer of the rectum

primary objectives: i. determine the maximum tolerated dose of oxaliplatin when combined with fluorouracil and external beam radiotherapy in patients with locally advanced adenocarcinoma of the rectum. (phase i closed to accrual effective 03/27/2003). ii. determine the pathological response rate in patients treated with this preoperative regimen and surgical resection. iii.determine the late toxicity of this preoperative regimen in these patients. iv. determine, in a preliminary manner, the progression-free survival, local control, and overall survival in patients treated with this regimen. outline: this is a dose-escalation, multicenter study of oxaliplatin. patients receive oxaliplatin iv over 1 hour on day 1, fluorouracil iv continuously on days 1-7, and radiotherapy on days 1-5. treatment repeats weekly for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of oxaliplatin until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. once the mtd is determined, additional patients are treated at that dose level in the phase ii portion of the study. (phase i closed to accrual effective 03/27/2003). patients may undergo radical resection of rectal tumor within 4-6 weeks after completion of chemoradiotherapy. patients are followed every 3 months for 2 years and then every 6 months for 3 years. projected accrual: a total of 9-24 patients will be accrued for phase i of the study (phase i closed to accrual effective 03/27/2003) and a total of 19 patients will be accrued for phase ii of the study within 12-18 months.

Eligibility criteria:
inclusion criteria: * histologically proven previously untreated adenocarcinoma of the rectum thatbegins within 12 cm of the anal verge by sigmoidoscopy and/or colonoscopy * locally advanced disease defined as any of the following: * fixed or immovable tumor on physical exam * t4 disease with invasion of adjacent structures (e.g., pelvic sidewall, sacral pelvis, bladder, or prostate) by ct scan, rectal ultrasound, or mri * t3 disease with invasion through the wall of the muscularis propria by transrectal ultrasound, ct scan, or mri * no distant metastatic disease * performance status - ecog 0-2 * granulocyte count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 * bilirubin no greater than upper limit of normal (uln) * sgot/sgpt no greater than 2.5 times uln * creatinine no greater than 1.5 mg/dl * creatinine clearance at least 60 ml/min * no active second malignancy except nonmelanomatous skin cancer or carcinoma in situ of the cervix * patients are not considered to have an active second malignancy if they have completed therapy and are at less than 30% risk of relapse * no prior or concurrent evidence of neuropathy * no history of allergy to platinum compounds or antiemetics * not pregnant or nursing * fertile patients must use effective contraception * no prior fluorouracil or platinum-based therapy for any malignancy * no other concurrent chemotherapy * hormonal therapy allowed only for non-disease related conditions (e.g., insulin for diabetes) or intermittently as an antiemetic (e.g., dexamethasone) * no prior pelvic irradiation * no concurrent antiretroviral therapy (haart) for hiv positive patients