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.

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.

• Authors: Yasuaki Arai, Atsushi Ohtsu, Yozo Sato, Takeshi Aramaki, Ken Kato, Madoka Hamada, Kei Muro, Yasuhide Yamada, Yoshitaka Inaba, Yasuhiro Shimada, Narikazu Boku, Yoshito Takeuchi, Sojiro Morita, Mitsuo Satake
• Journal: Journal of vascular and interventional radiology : JVIR (J Vasc Interv Radiol) Vol. 23 Issue 10 Pg. 1261-7 (Oct 2012) ISSN: 1535-7732 [Electronic] United States
• PMID: 22922040 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

Chemical References

• Irinotecan
• Fluorouracil
• Camptothecin

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Camptothecin (administration & dosage, analogs & derivatives)
• Colorectal Neoplasms (mortality, 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, drug therapy, mortality, secondary)
• Male
• Middle Aged
• Prospective Studies
• Radiography, Interventional
• Time Factors
• Treatment Outcome