Capecitabine, Oxaliplatin, and Gefitinib in Treating Patients With Metastatic Colorectal Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed* colorectal cancer

  • Metastatic disease
  • The site of the primary tumor must have been confirmed endoscopically, radiologically, or surgically to be the colon or rectum NOTE: *Confirmation is not required for recurrent metastatic disease unless an interval of > 5 years has elapsed between the initial primary surgery and the development of metastases

• Measurable disease

  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• No CNS metastases

PATIENT CHARACTERISTICS:

Age

• 18 to 80

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL (transfusion allowed)

Hepatic

• AST and ALT ≤ 3 times upper limit of normal (ULN)
• Bilirubin ≤ ULN
• No unstable or uncompensated hepatic disease

Renal

• Creatinine < 1.5 times ULN OR
• Creatinine clearance > 60 mL/min
• No unstable or uncompensated renal disease

Cardiovascular

• No unstable or uncompensated cardiac disease

Pulmonary

• No evidence of clinically active interstitial lung disease

  • Asymptomatic patients with chronic stable radiographic changes are eligible
• No unstable or uncompensated respiratory disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• No known hypersensitivity to gefitinib or any of its excipients
• No known hypersensitivity to platinum compounds, fluorouracil, or capecitabine
• No severe or uncontrolled systemic disease
• Able to receive oral medication
• No known dihydropyrimidine dehydrogenase (DPD) deficiency

• No known peripheral neuropathy ≥ grade 1

  • Absence of deep tendon reflexes as the sole neurological abnormality allowed
• No other significant clinical disorder or laboratory finding that would preclude study participation
• No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix (phase II only)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy for metastatic colorectal cancer (phase I)

• No prior chemotherapy for metastatic disease (phase II)

  • Prior fluorouracil and leucovorin calcium in the adjuvant setting allowed provided the last treatment was administered more than 6 months before the development of metastatic disease
• No prior irinotecan and oxaliplatin (phase II)

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy for colorectal cancer

Surgery

• See Disease Characteristics
• More than 4 weeks since prior major surgery (e.g., laparotomy)

Other

• Recovered from all prior therapy (no unresolved chronic toxicity > grade 2)
• More than 4 weeks since prior investigational drugs
• No prior epidermal growth factor receptor inhibitor therapy (phase II)
• No concurrent phenytoin, carbamazepine, rifampin, barbiturates, or Hypericum perforatum (St. John's wort)
• No other concurrent investigational drugs
• No other concurrent systemic therapy for colorectal cancer