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Isolated Hepatic Perfusion for the Treatment of Patients With Colorectal Cancer Liver Metastases After Irinotecan-Based Therapy

Surgical Metabolism Section, Surgery Branch, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Building 10, Room 4W-5940, Bethesda, Maryland 20892-1502

Correspondence: Address correspondence and reprint requests to: H. Richard Alexander, Jr., MD; E-mail: richard_alexander{at}nih.gov.

Background: Irinotecan given with 5-fluorouracil and leucovorin is currently used as first-line therapy for patients with metastatic colorectal cancer (CRC). However, the response duration is <1 year, and second-line systemic chemotherapy has limited efficacy. We analyzed the efficacy of isolated hepatic perfusion (IHP) for patients with progressive CRC liver metastases after irinotecan.

Methods: Between March 1993 and February 2003, 124 patients with CRC liver metastases underwent IHP on institutional review board–approved protocols. The overall treatment mortality was 4% (5 of 124). Twenty-five patients (10 women and 15 men; mean age, 53 years) were identified who had progressive liver metastases by carcinoembryonic antigen, imaging studies, or both after irinotecan. A 1-hour hyperthermic IHP (mean hepatic temperature, 40.0°C) with melphalan 1.5 mg/kg (mean total dose, 100 mg) was administered via laparotomy. Perfusion with an oxygenated extracorporeal circuit was established with inflow via a cannula in the gastroduodenal artery and common hepatic artery inflow occlusion. Outflow was via a cannula in an isolated segment of the inferior vena cava. During IHP, portal and inferior vena caval flow were shunted to the axillary vein. Patients were assessed for radiographical response, recurrence pattern, and survival.

Results: The mean number of prior irinotecan cycles in 25 patients was 6 (range, 2–14), and it was given primarily as second-line therapy. The median number of liver metastases before IHP was 10 (range, 1–50), and the median percentage of hepatic replacement by tumor was 25%. The mean operative time was 9 hours (range, 6–12 hours), and the median hospital stay was 11 days (range, 8–76 days). There was 1 complete response and there were 14 partial responses in 25 patients (60%), with a median duration of 12 months (range, 5–35 months). Disease progressed systemically in 13 of 25 patients at a median of 5 months (range, 3–16 months). The median overall survival was 12 months (range, 1–47 months), and the 2-year survival was 28%.

Conclusions: For patients with progressive CRC liver metastases after irinotecan, IHP has good efficacy in terms of response rate and duration. Continued evaluation of IHP with melphalan as second-line therapy in this clinical setting is justified.

Key Words: Metastatic colorectal cancer • Isolated hepatic perfusion • Liver metastases • Melphalan • Hyperthermia

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