Phase II Study of Treatment Selection Based Upon Tumor Thymidylate Synthase Expression in Previously Untreated Patients With Metastatic Colorectal Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of colorectal adenocarcinoma

- Metastatic or locally recurrent disease

- Measurable disease

- At least 2 formalin-fixed paraffin embedded core needle biopsies OR fine needle
aspirate containing a minimum of 3 clusters of malignant cells and fixed tissue from
the previous biopsy

- If no tissue samples are available the patient must be willing to undergo biopsy
of a metastatic site

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- PT (INR) ≤ 1.5 unless patient is receiving full-dose anticoagulants AND the following
criteria are met:

- In-range INR (usually between 2 and 3) AND on a stable dose of warfarin or low
molecular weight heparin

- No active bleeding or pathological condition that is associated with a high risk
of bleeding

- PTT < 1.5 times upper limit of normal (ULN)

- ALT and AST < 3 times ULN

- Bilirubin ≤ 1.5 times ULN

- No hepatic disease that would preclude study therapy

Renal

- Creatinine ≤ 1.8 mg/dL

- Meets 1 of the following criteria:

- Protein negative on urine dipstick

- Urine protein/creatinine ratio < 1.0

- Less than 2 g protein on 24-hour urine collection

- No renal disease that would preclude study therapy

Cardiovascular

- No arterial thromboembolic events within the past 6 months, including the following:

- Transient ischemic attack

- Cerebrovascular accident

- Unstable angina pectoris

- Myocardial infarction

- Patients with a history of hypertension must meet the following criteria:

- Blood pressure < 150/90 mm Hg

- Stable regimen of anti-hypertensive therapy

- No symptomatic arrhythmia

- No symptomatic congestive heart failure

- No clinically significant peripheral artery disease

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

- No other cardiovascular disease that would preclude study therapy

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study
participation

- Prior non-colorectal malignancies are allowed provided the following criteria are
met:

- No current clinical evidence of persistent or recurrent disease

- No active therapy for non-colorectal malignancy, including hormonal therapy

- No serious nonhealing wound, ulcer, or bone fracture within the past 28 days

- No significant traumatic injury within the past 28 days

- No neuropathy ≥ grade 2

- No other nonmalignant systemic disease that would preclude study therapy

- No ongoing or active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

- No prior chemotherapy for metastatic disease

- Adjuvant therapy completed at least 12 months before first evidence of
metastasis allowed

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- More than 28 days since prior major surgery

- More than 28 days since prior open biopsy