RATIONALE: 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 effective treatment for rectal cancer.

PURPOSE: Phase I trial to study the effectiveness of radiation therapy plus chemotherapy followed by surgery and additional chemotherapy in treating patients who have advanced nonmetastatic primary cancer of the rectum.

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of oxaliplatin when combined preoperatively with concurrent radiotherapy and fluorouracil in patients with locally advanced rectal adenocarcinoma.
• Evaluate the resection rate for T4 rectal cancers, the pathological complete response rate for T3 and T4 rectal cancers, and the expected vs actual type of resection (abdominoperineal resection vs low anterior resection [LAR] vs LAR/coloanal anastomosis) in patients treated with this regimen.
• Determine survival and patterns of recurrence in this patient population after this treatment regimen.
• Evaluate anastomotic and sphincter function in these patients after preoperative combined modality therapy.

OUTLINE: This is a dose-escalation study of preoperative oxaliplatin.

Patients receive fluorouracil IV continuously with concurrent radiotherapy for 5.5 weeks. Patients also receive oxaliplatin IV over 2 hours on day 1 of weeks 1, 3, and 5.

Cohorts of 5 patients each receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 5 patients experience dose-limiting toxicity. Additional patients are treated at the MTD.

Patients undergo surgery 6-8 weeks after completing preoperative chemotherapy and radiotherapy. The surgical procedure is determined by the extent of the tumor before preoperative therapy. The type of operative procedure may be abdominoperineal resection, low anterior resection (LAR), or LAR/coloanal anastomosis.

Postoperative chemotherapy begins within 6 weeks after surgery, comprising leucovorin calcium and fluorouracil IV on days 1-5. Treatment repeats every 21 days for 4 courses.

Patients are followed every 3 months for 2.5 years, every 6 months for 3 years, then annually for 5 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 1 year.

• Drug: fluorouracil
• Drug: leucovorin calcium
• Drug: oxaliplatin
• Procedure: adjuvant therapy
• Procedure: conventional surgery
• Procedure: neoadjuvant therapy
• Radiation: radiation therapy

• Rosenthal DI, Catalano PJ, Haller DG, Landry JC, Sigurdson ER, Spitz FR, Benson AB 3rd. Phase I Study of Preoperative Radiation Therapy With Concurrent Infusional 5-Fluorouracil and Oxaliplatin Followed by Surgery and Postoperative 5-Fluorouracil Plus Leucovorin for T3/T4 Rectal Adenocarcinoma: ECOG E1297. Int J Radiat Oncol Biol Phys. 2008 Sep 1;72(1):108-13.
• Ryan DP. Rectal cancer: integrating oxaliplatin into chemoradiation studies. Oncology (Huntingt). 2000 Dec;14(12 Suppl 11):38-41. Review.

DISEASE CHARACTERISTICS:

• Histologically confirmed locally advanced, nonmetastatic primary adenocarcinoma of the rectum

  • Stage II or III (T3 or T4)
  • Clinically resectable OR

  • Clinically fixed or initially not completely resectable (T4, N0-2, M0) based on the presence of at least one of the following criteria:

    • Clinically fixed tumor on rectal exam with tumor adherent to the pelvic sidewall or sacrum
    • Sciatica attributed to sacral root invasion with CT scan/MRI evidence of lack of clear tissue plane as evidence of fixation
    • Hydronephrosis on CT scan or IVP, or ureteric or bladder invasion by cystoscopy and cytology or biopsy, or invasion into prostate
    • Vaginal or uterine involvement

• No tumor outside of the pelvis, including:

  • Liver metastases
  • Peritoneal seeding
  • Metastatic inguinal lymphadenopathy
• Distal border of tumor must be at or below the peritoneal reflection, defined as within 12 cm of anal verge by proctoscopic exam
• Transmural penetration through the muscularis propria demonstrated by CT scan plus endorectal ultrasound or MRI
• No high-grade (lumen diameter less than 1 cm) large bowel obstruction, unless diverting colostomy has been performed

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL
• Alkaline phosphatase no greater than 2 times upper limit of normal (ULN)
• SGOT no greater than 2 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Other:

• Caloric intake at least 1500 kilocalories per day
• No other prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No active inflammatory bowel disease
• No other serious medical illness
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior pelvic radiotherapy
• No concurrent intraoperative radiotherapy or brachytherapy

Surgery:

• Not specified