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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00492999.

Figure 1

Waterfall plot illustrating the percentage decrease in tumor size after treatment with hepatic arterial infusion of floxuridine/dexamethasone + best sytemic therapy. Blue bars represent patients who had not received prior systemic chemotherapy. Dashed line separates responders and non-responders by WHO criteria

Figure 2

Overall (A) and progression free (B) survival in 49 patients treated with HAI and systemic chemotherapy. Survival was calculated since treatment start. Graphs depict all patients (green line) and stratified by prior therapy (blue: chemo naïve; red: previously treated).

Figure 3

Landmark analysis. Time zero means 12 months from start of treatment. (A) Overall survival- 4 patients without 12 months follow up were excluded. P=0.005; (B) Progression-free survival-23 patients without 12 months follow up were excluded. P=0.60; (c) Time to hepatic progression- 18 patients without 12 months follow up were excluded. P=0.96