Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes.

PURPOSE: Evaluate conversion rate of patients with unresectable colorectal-liver metastasis to complete resection with hepatic-arterial infusion plus systemic chemotherapy including bevacizumab (Bev). PATIENTS AND METHODS: Forty-nine patients with unresectable colorectal liver metastases (CRLM) were included in a single-institution phase II trial. Conversion to resection was the primary outcome. Secondary outcomes included overall survival (OS), progression-free survival, and response rates. Multivariate and landmark analyses were performed to evaluate survival differences between resected and nonresected patients.
RESULTS: Median number of tumors was 14 and 65% were previously treated patients. A high biliary toxicity rate was found in the first 24 patients whose treatment included Bev. The remaining 25 patients were treated without Bev. Overall response rates were 76% (4 complete responses). Twenty-three patients (47%) achieved conversion to resection at a median of 6 months from treatment initiation. Median OS and progression-free survival for all patients were 38 (95% confidence interval: 28 to not reached) and 13 months (95% confidence interval: 7-16). Bev administration did not impact outcome. Conversion was the only factor associated with prolonged OS and progression-free survival in multivariate analysis. On landmark analysis, patients who had undergone resection had longer OS than those who did not undergo resection (3-year OS: 80% vs 26%). Currently, 10 of 49 (20%) patients have no evidence of disease (NED) at a median follow-up of 39 months (32-65 months).
CONCLUSIONS: In patients with extensive unresectable CRLM, the majority of whom were previously treated, 47% were able to undergo complete resection after combined HAI and systemic therapy. Conversion to resection is associated with prolonged survival.