GM-CSF and Combination Chemotherapy in Treating Patients Who Are Undergoing Surgery for Stage II or Stage III Colon Cancer

OBJECTIVES:

Primary

• Determine the safety of neoadjuvant and adjuvant sargramostim (GM-CSF) and adjuvant chemotherapy in patients with resectable stage II or III colon cancer.
• Determine the efficacy, in terms of enhanced tumor-associated macrophage response, of this regimen in these patients.

Secondary

• Determine overall survival and time to progression in patients treated with this regimen.

OUTLINE:

• Neoadjuvant therapy and surgery: Patients receive sargramostim (GM-CSF) subcutaneously (SC) once daily beginning between days -16 and -12 and continuing until day -1. Patients undergo surgical resection on day 0. Patients with stage I or IV disease are removed from the study. All other patients proceed to adjuvant chemotherapy or observation.
• Adjuvant chemotherapy or observation: Patients with high-risk stage II or any stage III disease are assigned to group 1 or 2. Patients with low-risk stage II disease are assigned to group 3.

• Group 1 (adjuvant therapy for high-risk stage II disease): Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV on days 1, 8, 15, 22, 29 and 36. Patients also receive GM-CSF SC once daily on days 50-54. Treatment repeats every 56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
• Group 2 (adjuvant therapy for stage III disease): Patients receive adjuvant chemotherapy and GM-CSF as in group 1. Alternatively, patients may receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. These patients also receive GM-CSF SC once daily on days 10-14 of every fourth course. Treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
• Group 3 (low-risk stage II disease): Patients undergo observation only every 3 months.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon

• Stage II or III disease
• No carcinoma in situ
• No perforated or obstructed tumors
• No dual primary lesions by colonoscopy or barium enema
• Resectable disease

• Distal and proximal bowel end must be > 5 cm from tumor
• Tumor must not extend below peritoneal reflection
• No distant intra-abdominal metastases (even if resected)
• No rectal cancer

• No tumors that require opening of the pelvic peritoneum to define the extent of disease

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 2.0 mg/dL

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No uncontrolled cardiac arrhythmia

Immunologic

• No ongoing or active infection
• No allergy to yeast or yeast-based products
• No allergy to sargramostim (GM-CSF)
• No allergy to fluorouracil
• No allergy to leucovorin calcium

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of Crohn's disease
• No history of ulcerative colitis
• No other malignancy within the past 3 years except superficial squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Chemotherapy

• No prior chemotherapy, including fluorouracil, for colon cancer
• No other concurrent chemotherapy

Radiotherapy

• No prior radiotherapy for colon cancer
• No concurrent radiotherapy

Other

• No other prior therapy for colon cancer
• No concurrent immunosuppressant therapy
• No other concurrent investigational agents
• No other concurrent anticancer therapy