OBJECTIVES:

• Determine the 4-month progression-free survival rate in patients with recurrent metastatic colorectal adenocarcinoma treated with gefitinib.
• Determine the objective tumor response rate, progression, and overall survival of patients treated with this drug.
• Determine the toxicity of this drug in these patients.

OUTLINE: This is a randomized, double-blind study. Patients are stratified according to ECOG performance status (0-1 vs 2), baseline serum CEA (less than 5 mg/L vs at least 5 mg/L), and number of metastatic sites (1 vs 2 or more). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral gefitinib once daily (twice daily on day 1 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive a higher dose of oral gefitinib as in arm I. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven adenocarcinoma of the colon or rectum
• Measurable disease
• Evidence of new or progressive metastatic disease within 6 months of last treatment
• Must have received prior systemic treatment with fluorouracil (and/or its analogs, with or without leucovorin calcium or levamisole) and irinotecan in the adjuvant or metastatic setting
• Metastatic tumor site accessible for biopsy
• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST or ALT no greater than 2.5 times ULN (5 times ULN if tumor involvement of the liver)

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No New York Heart Association class III or IV heart disease
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing active or uncontrolled infections
• Other prior malignancies allowed provided prior therapy is discontinued and no evidence of disease
• No other uncontrolled illness or psychiatric illness/social situations that would preclude study
• Must be able to take and retain oral medications

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior signal transduction inhibitors (e.g., vascular endothelial growth factor-, vascular endothelial growth factor receptor-, and epidermal growth factor receptor-targeted agents) for colorectal cancer

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy and recovered
• No other prior cytotoxic chemotherapy (e.g., oxaliplatin) for colorectal cancer

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• Not specified

Other:

• No other prior systemic therapy for colorectal cancer
• No other prior investigational or approved agents for colorectal cancer
• No other concurrent investigational agents
• No concurrent antiretroviral therapy for HIV-positive patients