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)