Conversion to resectability using hepatic artery infusion plus systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma

Abstract

PURPOSE To determine the conversion to resectability in patients with unresectable liver metastases from colorectal cancer treated with hepatic arterial infusion (HAI) plus systemic oxaliplatin and irinotecan (CPT-11). PATIENTS AND METHODS Forty-nine patients with unresectable liver metastases (53% previously treated with chemotherapy) were enrolled onto a phase I protocol with HAI floxuridine and dexamethasone plus systemic chemotherapy with oxaliplatin and irinotecan. Results Ninety-two percent of the 49 patients had complete (8%) or partial (84%) response, and 23 (47%) of the 49 patients were able to undergo resection in a group of patients with extensive disease (73% with > five liver lesions, 98% with bilobar disease, 86% with > or = six segments involved). For chemotherapy-naïve and previously treated patients, the median survival from the start of HAI therapy was 50.8 and 35 months, respectively. The only baseline variable significantly associated with a higher resection rate was female sex. Variables reflecting extensive anatomic disease, such as number of lesions or number of vessels involved, were not significantly associated with the probability of resection. CONCLUSION The combination of regional HAI floxuridine/dexamethasone and systemic oxaliplatin and irinotecan is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, demonstrating a 47% conversion to resection (57% in chemotherapy-naïve patients). Future randomized trials should compare HAI plus systemic chemotherapy with systemic therapy alone to assess the additional value of HAI therapy in converting patients with hepatic metastases to resectability.

Fig 1.

A patient with extensive disease involving all vessels who, after response, was able to undergo resection. Carcinoembryonic antigen decreased from 156 to 2.9. Patient still has no recurrence 2 years after resection.

Fig 2.

Waterfall graph depicting the decrease in tumor measurements from baseline in patients treated with hepatic arterial infusion floxuridine/dexamethasone plus systemic oxaliplatin/irinotecan. −100 means 100% decrease in tumor. Blue bars represent patients who were not able to undergo resection. Gold bars represent patients who, though initially unresectable, after response with hepatic arterial infusion and systemic chemotherapy were able to undergo resection.

Fig 3.

Median survival differences in patients who were either chemotherapy-naïve (50.8 months) or who had received previous systemic chemotherapy (35 months). Chemo, chemotherapy; N, no; Y, yes.