Oxaliplatin, Leucovorin, and Fluorouracil Before and After Radiation Therapy and Surgery in Treating Patients With Rectal Cancer That Can Be Removed by Surgery (COPERNICUS)

DISEASE CHARACTERISTICS:

• Histopathologically confirmed rectal adenocarcinoma meeting the following criteria:

  • Inferior aspect of tumor is > 4 cm from anal verge on digital examination and pelvic MRI scan
  • Superior aspect of tumor is not higher than the anterior aspect of the S1/S2 interspace on pelvic MRI scan
  • Mesorectal fascia is not threatened or involved (tumor > 1 mm from mesorectal fascia)

  • Primary tumor meets 1 of the following criteria:

    • T3a-b (mesorectal primary tumor invasion seen ≤ 5 mm beyond muscularis propria) in the presence of 1 of the following:

      • Extra-mural vascular invasion
      • Mesorectal lymph node(s)/tumor deposit(s) with irregular border and mixed signal intensity
    • Any T3c (primary tumor invasion seen > 5 mm beyond muscularis propria)-T4a (invasion of visceral peritoneum for tumors with a component above peritoneal reflection)
  • Low tumors should not involve levator ani (> 1 mm gap between tumor and levator ani) or anal sphincters
• No evidence of distant metastases or stage T4b cancer with invasion into adjacent organs or structures
• Must have measurable disease at the baseline visit
• Impending rectal obstruction is permitted if relieved by a non-functioning ileostomy or colostomy
• No disease threatening mesorectal fascia (disease ≤ 1 mm from mesorectal fascia whether this is primary tumor, extra-mural vascular invasion, or tumor deposit with irregular border and mixed signal intensity)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Hemoglobin ≥ 9 g/dL
• WBC ≥ 3 x 10^9/L
• Absolute neutrophil count ≥ 1.5 x10^9/L
• Platelet count ≥ 100 x10^9/L
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 x ULN
• AST or ALT ≤ 2.5 x ULN
• Creatinine clearance ≥ 50 mL/min
• Magnesium and calcium normal
• Candidate for systemic therapy, in the opinion of the primary oncologist
• No known significant impairment of intestinal absorption (e.g., chronic diarrhea, inflammatory bowel disease)
• No evidence of established or acute ischemic heart disease (e.g., left bundle branch block, pathological q-waves, ST elevation, or ST-segment depression) and normal clinical cardiovascular assessment by ECG
• No enlarged pelvic sidewall lymph nodes
• No severe local bowel symptoms of tenesmus or irregularity or frequency of bowel habit precluding accurate assessment of diarrhea
• No pelvic sepsis
• No uncontrolled infection
• Not pregnant or nursing
• Fertile patients must use effective contraception during treatment and for 6 months after completion of treatment
• No other prior or current malignant disease that, in the judgement of the treating investigator, is likely to interfere with study treatment or assessment of response

• No clinically significant cardiovascular disease, including any of the following within the past year:

  • Myocardial infarction
  • Unstable angina
  • Symptomatic congestive heart failure
  • Serious uncontrolled cardiac arrhythmia
• No history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease)

PRIOR CONCURRENT THERAPY:

• No prior pelvic radiotherapy
• No metallic colon stent or rectal stent in situ
• More than 30 days since prior chemotherapy, radiotherapy, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloproteinase inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibodies, or other experimental drugs