A Phase I Study Of Hepatic Arterial Infusion With Floxuridine And Dexamethasone In Combination With Intravenous Oxaliplatin Plus 5-Fluorouracil And Leucovorin In Patients With Unresectable Hepatic Metastases From Colorectal Cancer

OBJECTIVES:

• Determine the maximum tolerated dose of oxaliplatin and fluorouracil when given with leucovorin calcium and hepatic intra-arterial floxuridine and dexamethasone with or without cryosurgery (group I cryosurgery closed to accrual as of 10/13/03) in patients with unresectable liver metastases from colorectal cancer.
• Determine, preliminarily, the anti-tumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of oxaliplatin and fluorouracil. Patients are assigned to one of two treatment groups. (Group I closed to accrual as of 10/13/03.)

• Group I (closed to accrual as of 10/13/03): Patients with no more than 8 hepatic metastases and no metastases greater than 5 cm in diameter undergo cryosurgery prior to chemotherapy. Chemotherapy is delayed for at least 4 weeks after cryosurgery.
• Group II: Patients with more than 8 hepatic metastases or at least one metastases greater than 5 cm in diameter do not undergo cryosurgery prior to chemotherapy.

Beginning 2 weeks after pump placement surgery, all patients receive floxuridine and dexamethasone by hepatic intra-arterial infusion continuously on days 1-14; oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on days 15 and 29; and fluorouracil IV continuously over 48 hours on days 15-16 and 29-30. Courses repeat every 36 days in the absence of disease progression or unacceptable toxicity.