Time Finding Study of Chronomodulated Irinotecan, 5 Fluorouracil, Leucovorin and Oxaliplatin as First or Second Chemotherapy Line Against Metastatic Colorectal Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed colorectal cancer

- Unresectable metastatic or locoregional disease

- At least 1 measurable lesion outside a previously irradiated area or an area treated
with physical devices (e.g., cryotherapy, laser, or thermoablation)

- No prior enrollment in EORTC-05963

- No symptomatic brain metastases

PATIENT CHARACTERISTICS:

Age:

- Over 18

Performance status:

- WHO 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Neutrophil count greater than 2,000/mm^3

- Platelet count at least 90,000/mm^3

Hepatic:

- Bilirubin no greater than 2 times upper limit of normal (ULN)

Renal:

- Creatinine no greater than 1.5 times ULN

- No uncontrolled hypercalcemia

Cardiovascular:

- No overt cardiac disease

Pulmonary:

- No severe respiratory illness

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Male patients must use effective barrier contraception during and for up to 6 months
after study

- No baseline diarrhea greater than grade I (must have less than 4 stools per 24 hours)

- No prior grade III or IV toxicity related to irinotecan

- No sensory or motor neuropathy with functional impairment

- No prior hypersensitivity to any study drug

- No other primary tumor except basal cell skin cancer or carcinoma in situ of the
cervix

- No uncontrolled infectious or chronic disease

- No psychological, familial, sociological, or geographical condition that would
preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No concurrent prophylactic growth factor therapy

Chemotherapy:

- At least 1 month since prior chemotherapy

- No prior irinotecan, fluorouracil, leucovorin calcium, and oxaliplatin as combination
therapy

- Other prior therapy containing irinotecan and/or oxaliplatin allowed

- No more than 1 prior chemotherapy regimen for metastatic or locoregional disease

- Adjuvant chemotherapy considered first-line therapy if tumor relapsed within 6 months
of completion of therapy

Endocrine therapy:

- No concurrent corticosteroids except for emergencies

Radiotherapy:

- See Disease Characteristics

- Palliative radiotherapy for bone lesion allowed except for disease progression

Surgery:

- See Disease Characteristics