A Phase I Study Of ZD1839 (Iressa) In Combination With Irinotecan, Leucovorin, And 5-Fluorouracil In Previously Untreated, Stage IV Colorectal Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed adenocarcinoma of the colon or rectum

- Locally advanced, locally recurrent, or metastatic disease

- Not curable by surgery and/or not amenable to radiotherapy with curative intent

- Histological or cytological confirmation of metastatic cancer not required for
patients with prior surgically resected colorectal cancer if more than 5 years
elapsed between primary surgery and development of metastatic disease OR if
primary cancer was stage I or II

- Prior adjuvant therapy with fluorouracil or immunotherapy for resected stage II, III,
or IV disease allowed

- Measurable disease

- No known brain metastases

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-1

Life expectancy:

- More than 12 weeks

Hematopoietic:

- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- Bilirubin normal

- AST/ALT no greater than 5 times upper limit of normal

Renal:

- Creatinine normal

Cardiovascular:

- No uncontrolled high blood pressure

- No unstable angina

- No symptomatic congestive heart failure

- No myocardial infarction within the past 6 months

- No serious uncontrolled cardiac arrhythmia

- No New York Heart Association class III or IV heart disease

Other:

- No active or uncontrolled infection

- No predisposing colonic or small bowel disorders with uncontrolled symptoms as
indicated by more than 3 loose stools daily in patients without a colostomy or
ileostomy

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or adequately treated noninvasive carcinomas

- No other concurrent medical or psychiatric condition that would preclude study

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 12 months since prior immunotherapy

Chemotherapy:

- At least 12 months since prior fluorouracil

- No prior chemotherapy for advanced colorectal cancer

- No prior irinotecan

Radiotherapy:

- No prior radiotherapy to more than 15% of bone marrow

- At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative
radiotherapy)

- No concurrent radiotherapy

Surgery:

- At least 4 weeks since prior major surgery (e.g., laparotomy) and recovered

- At least 2 weeks since prior minor surgery and recovered

- No concurrent ophthalmic surgery

Other:

- No prior ZD 1839

- No other concurrent investigational or commercial agents or therapies for malignancy

- No concurrent combination antiretroviral therapy for HIV

- No concurrent oral retinoids

- No concurrent prochlorperazine on day of irinotecan administration