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