Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer

Purpose : Patients who undergo resection of liver metastases from colorectal cancer have an average 2-year survival of 65%. With hepatic arterial infusion (HAI) plus systemic fluorouracil and leucovorin, 2-year survival increased to 86%. For further improvement in both local and systemic control, combinations of new systemic drugs with HAI are being explored. The purpose of this study was to determine the maximum-tolerated dose (MTD) of systemic irinotecan (CPT-11) and HAI floxuridine (FUDR) plus dexamethasone (DEX) as combination adjuvant therapy after liver resection. Patients and Methods: Ninety-six patients who underwent complete resection of liver metastases from colorectal cancer were treated with six monthly cycles of HAI FUDR plus DEX for 14 days of each 4-week cycle plus escalating doses of systemic CPT-11. The primary end points of the phase 1/11 study were the MTD and efficacy of this regimen. Results: The MTD for combined systemic CPT-11 and HAI FUDR was CPT-11 at 200 mg/m(2) every other week and FUDR at 0.12 mg/kg x pump volume divided by pump flow rate. The dose-limiting toxicities were diarrhea and neutropenia. With a median follow-up time of 26 months, the 2-year survival rate is 89%. All of the 27 patients who were treated at the MTD are alive. Conclusion: In patients who undergo resection of liver metastases from colorectal cancer, adding systemic CPT-11 to HAI therapy in an adjuvant regimen is feasible. This regimen seems to have comparable activity to fluorouracil and leucovorin, but further studies are needed to assess whether it improves local control or decreases extrahepatic recurrences. (C) 2003 by American Society of Clinical Oncology.