FOLFOXIRI Compared With FOLFIRI for Metastatic Colorectal Cancer

Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) as First-line Treatment for Metastatic Colorectal Cancer

The purpose of the study is to evaluate if the exposure to all the three active cytotoxic agents (FOLFOXIRI regimen) is superior in terms of response rate to conventional chemotherapy with the FOLFIRI regimen as first-line treatment of metastatic colorectal cancer patients.

Survival of patients with metastatic colorectal cancer is correlated with the proportion of patients who receive all the three active drugs in the course of the disease, but not with the proportion of patients who receive any second-line therapy. In a sequential strategy, not all patients who progress after first-line chemotherapy are able to receive second-line treatment. Moreover, there is a correlation between the response rate to chemotherapy and the postchemotherapy radical resection rate of metastases.

Therefore, a way to improve the outcome of metastatic colorectal cancer patients could be to administer a first-line regimen containing the three active agents.

Inclusion Criteria:

• adenocarcinoma of the colon or rectum
• unresectable metastatic disease
• age 18 to 75 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower if age 70 years or younger or ECOG performance status of 0 if age 71 to 75 years measurable disease according to WHOcriteria
• leukocyte count of at least 3,500/mm3, neutrophils count of at least 1,500/mm3, platelet count of at least 100,000/mm3
• serum creatinine of 1.3 mg/dL or less
• serum bilirubin less than 1.5 mg/dL and AST, ALT, and alkaline phosphatase 2.5 x normal values or less (</= 5 if liver metastases)
• previous fluoropyrimidine-based adjuvant chemotherapy was allowed if ended more than 6 months before random assignment

Exclusion Criteria:

• previous palliative chemotherapy for metastatic disease
• previous chemotherapy including irinotecan or oxaliplatin
• symptomatic cardiac disease, myocardial infarction in the last 24 months or uncontrolled arrhythmia
• active infections
• inflammatory bowel disease
• total colectomy