Irinotecan or Fluorouracil Plus Leucovorin in Treating Patients With Previously Treated Metastatic Colorectal Cancer

OBJECTIVES:

- Determine the tumor response rate in patients receiving irinotecan or fluorouracil and
leucovorin calcium for metastatic colorectal cancer previously treated with oxaliplatin
with or without irinotecan.

- Determine the time to tumor progression, time to treatment failure, and overall
survival of patients treated with these regimens.

- Determine the toxic effects of these regimens in these patients.

- Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to prior
chemotherapy (oxaliplatin-based therapy vs irinotecan and oxaliplatin combination therapy).
Patients are assigned to one of two treatment groups.

- Group I (prior oxaliplatin-based chemotherapy): Patients receive irinotecan IV over 90
minutes on day 1. Treatment repeats every 3 weeks.

- Group II (prior irinotecan and oxaliplatin combination chemotherapy): Patients receive
leucovorin calcium IV over 2 hours and fluorouracil IV continuously on days 1 and 2.
Treatment repeats every 2 weeks.

- Both groups: Treatment continues in the absence of disease progression or unacceptable
toxicity. Patients with a confirmed complete response for 2 consecutive courses may
discontinue treatment at investigator's discretion.

Quality of life is assessed at baseline, approximately every 6 weeks during treatment, and
then after the last course of treatment.

Patients are followed every 3 months for 5 years.

DISEASE CHARACTERISTICS:

- Diagnosis of metastatic colorectal adenocarcinoma incurable by surgery or not
amenable to radiotherapy with curative intent

- Progressive disease after one of the following prior treatments for metastatic
disease:

- Oxaliplatin-based chemotherapy

- Irinotecan and oxaliplatin combination chemotherapy

- At least 1 measurable lesion

- At least 20 mm in at least one dimension

- No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- At least 12 weeks

Hematopoietic:

- Absolute neutrophil count at least 2,000/mm^3

- Platelet count at least 100,000/mm^3

Hepatic:

- Bilirubin no greater than 0.5 mg/dL above upper limit of normal (ULN)

- AST no greater than 5 times ULN

Renal:

- Creatinine no greater than 1.5 times ULN

Cardiovascular:

- No unstable angina

- No symptomatic congestive heart failure

- No serious uncontrolled cardiac arrhythmia

Other:

- No active or uncontrolled infection

- No evidence of other serious illness

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or noninvasive carcinomas

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No concurrent sargramostim (GM-CSF)

Chemotherapy:

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy

- No more than 1 prior chemotherapy regimen for advanced colorectal cancer

- Prior adjuvant chemotherapy allowed

Endocrine therapy:

- Not specified

Radiotherapy:

- See Disease Characteristics

- No prior radiotherapy to more than 25% of bone marrow

Surgery:

- See Disease Characteristics

- At least 4 weeks since prior major surgery