A Multicenter, Open-Label, Randomized, Two-Arm Study of Irinotecan (CPT-11) Versus the Combination of Oxaliplatin + Irinotecan (CPT-11) as Second-Line Treatment of Metastatic Colorectal Carcinoma

Inclusion Criteria

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