Inclusion Criteria

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)