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

Ann Surg. 2015 Feb;261(2):353-60. doi: 10.1097/SLA.0000000000000614.

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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / pathology*
  • Female
  • Floxuridine / administration & dosage
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Hepatectomy*
  • Hepatic Artery
  • Humans
  • Infusions, Intra-Arterial*
  • Irinotecan
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoadjuvant Therapy
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Prospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Floxuridine
  • Oxaliplatin
  • Bevacizumab
  • Irinotecan
  • Fluorouracil
  • Camptothecin

Associated data

  • ClinicalTrials.gov/NCT00492999