Irinotecan With or Without Oxaliplatin in Treating Patients With Metastatic Colorectal Cancer

OBJECTIVES:

• Compare the overall survival of patients with metastatic colorectal cancer treated with irinotecan with or without oxaliplatin.
• Compare the response rate, time to tumor-related worsening of symptoms, time to disease progression, onset and duration of responses, and duration of disease stabilization in these patients treated with these regimens.
• Compare the safety of these regimens in these patients.

OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to Karnofsky performance status (50-60% vs 70-100%), number of metastatic organs involved (1 vs 2 or more), lactic dehydrogenase (no greater than 1.5 times upper limit of normal (ULN) vs greater than 1.5 times ULN), and prior fluorouracil chemotherapy (adjuvant vs first-line treatment for metastatic disease). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive irinotecan IV over 90 minutes on day 1.
• Arm II: Patients receive oxaliplatin IV over 120 minutes followed by irinotecan IV over 30 minutes on day 1.

Courses repeat in each arm every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days, every 4 weeks for 3 months, and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 596 patients (298 per arm) will be accrued for this study within 18 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum
• Metastatic or recurrent disease that is not amenable to potentially curative treatment
• Progressive or recurrent disease during or after 1, and only 1, regimen of fluorouracil with or without leucovorin calcium or during or within 6 months after adjuvant chemotherapy with fluorouracil and leucovorin calcium

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 50-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT/SGPT no greater than 2 times ULN (no greater than 5 times ULN if liver metastases present)
• Alkaline phosphatase no greater than 2 times ULN (no greater than 5 times ULN if liver metastases present)

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No unstable angina
• No New York Heart Association class III or IV congestive heart failure
• No serious cardiac arrhythmia
• No history of cardiac toxicity from fluorouracil/leucovorin calcium
• No myocardial infarction within past 6 months

Pulmonary:

• No interstitial pneumonia or extensive and symptomatic fibrosis of the lung

Other:

• No uncontrolled predisposing colonic or small bowel disorder
• No prior chronic enteropathy, chronic diarrhea, or unresolved bowel obstruction/subobstruction
• No diabetes
• No active infection
• No known current peripheral neuropathy
• No concurrent active cancer except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No intolerance of appropriate antiemetics
• No history of anaphylaxis or potential intolerance to atropine sulfate or loperamide
• Not pregnant or nursing
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy
• No prior irinotecan or oxaliplatin
• No other prior chemotherapy agents except fluorouracil with or without leucovorin calcium as first-line therapy for metastatic disease or in the adjuvant setting

Endocrine therapy:

• Not specified

Radiotherapy:

• Prior radiotherapy to non-target lesions allowed
• No prior radiotherapy to target lesions unless disease progression is documented within the radiation port
• At least 3 weeks since prior radiotherapy

Surgery:

• At least 4 weeks since prior major surgical procedure and recovered
• Prior surgery for primary tumor or metastasis allowed

Other:

• At least 30 days since prior investigational drug
• No concurrent investigational agents