Phase I/II study of radiologic hepatic arterial infusion of fluorouracil plus systemic irinotecan for unresectable hepatic metastases from colorectal cancer: Japan Clinical Oncology Group Trial 0208-DI

J Vasc Interv Radiol. 2012 Oct;23(10):1261-7. doi: 10.1016/j.jvir.2012.06.031. Epub 2012 Aug 24.

Abstract

Purpose: Treatment of patients who have metastatic colorectal cancer (CRC) by using a combination of hepatic arterial infusion chemotherapy (HAIC) and systemic chemotherapy has resulted in promising clinical outcomes. Additionally, image-guided HAIC is reported to be less invasive and distribute drugs more accurately than surgical HAIC. The purpose of this study was to assess the combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan in a multicenter phase I/II study.

Materials and methods: Twenty-five patients with unresectable liver metastases from CRC were fitted with hepatic arterial catheter and port systems by using image-guided methods. Intraarterial fluorouracil (1,000 mg/m(2)) was administered on days 1, 8, and 15 of each treatment cycle. The dose of systemic irinotecan on days 1 and 15 was escalated from 75 mg/m(2).

Results: No dose-limiting toxicity was encountered during phase I, and the recommended dose of irinotecan was set at 150 mg/m(2). Grade 3 or higher adverse events included hyperglycemia (15%), elevated γ-glutamyl transpeptidase levels (15%), and neutropenia (9%). The response rate and median survival time were 72% and 49.8 months (95% CI, 27.5-78.1 mo), respectively.

Conclusions: The combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan yielded favorable safety, response rate, and survival results. This combination should be evaluated in a large study.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / secondary*
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Fluorouracil / administration & dosage
  • Hepatic Artery / diagnostic imaging*
  • Humans
  • Infusions, Intra-Arterial
  • Infusions, Intravenous
  • Irinotecan
  • Japan
  • Kaplan-Meier Estimate
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Prospective Studies
  • Radiography, Interventional*
  • Time Factors
  • Treatment Outcome

Substances

  • Irinotecan
  • Fluorouracil
  • Camptothecin