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