Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Gastrointestinal Cancer

DISEASE CHARACTERISTICS:

Biopsy confirmed diagnosis of gastrointestinal cancer

Advanced, unresectable disease
Confirmation of UGT1A1 TA indel genotype

Measurable or evaluable (non-measurable) disease

Measurable disease is defined as ≥ 1 lesion that can be accurately measured (longest diameter to be recorded) as ≥ 2.0 cm with conventional techniques or as ≥ 1.0 cm with spiral CT scan

Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules, palpable lymph nodes)
Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung

The following are considered non-measurable disease:

Bone lesions
Leptomeningeal disease
Ascites
Pleural/pericardial effusions
Lymphangitis cutis/ pulmonis
Inflammatory breast disease
Abdominal masses (not followed by CR scan or MRI)
Cystic lesions
All other lesions (or sites of disease), including small lesions (longest diameter < 2.0 cm with conventional techniques or as < 1.0 cm with spiral CT)
No known central nervous system metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Inclusion criteria

Life expectancy ≥ 12 weeks.
ECOG performance status 0-2
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
SGOT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if liver metastases)
Total Bilirubin ≤ ULN for patients in group 3 and ≤ 2.0 times ULN for patients in groups 1 and 2
Hemoglobin ≥ 9.0 g/dL
Creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception for the duration of study treatment
Willing to provide blood samples for mandatory translational studies

Exclusion criteria

Known allergy to irinotecan hydrochloride-related agents (e.g., topotecan), 5-fluorouracil, and/or leucovorin calcium
Active or uncontrolled infection
Evidence of serious intercurrent illness (e.g., unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia)

PRIOR CONCURRENT THERAPY:

Recovered from all toxicities
More than 4 weeks since prior major surgery

More than 2 weeks since completion of prior radiotherapy

No prior radiotherapy to > 25% of bone marrow
More than 2 week since prior cytotoxic chemotherapy, biologic therapy, or immunotherapy
No concurrent sargramostim (GM-CSF)