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01-02-2009 | Hepatobiliary and Pancreatic Tumors

A Phase I Study of Hyperthermic Isolated Hepatic Perfusion with Oxaliplatin in the Treatment of Unresectable Liver Metastases from Colorectal Cancer

Authors: Herbert J. Zeh III, MD, Charles K. Brown, MD, PhD, Matthew P. Holtzman, MD, Merrill J. Egorin, MD, Julianne L. Holleran, BS, Douglas M. Potter, PhD, David L. Bartlett, MD

Published in: Annals of Surgical Oncology | Issue 2/2009

Abstract

Isolated hepatic perfusion (IHP) is a proven approach for regional delivery of chemotherapy in patients with unresectable primary and metastatic tumors of the liver. Most trials of IHP have utilized melphalan as the active drug in the perfusate. We performed a phase I trial to evaluate the efficacy, safety, and maximum tolerated dose (MTD) of oxaliplatin delivered by hyperthermic isolated hepatic perfusion. A phase I dose-escalation trial of hyperthermic IHP with oxaliplatin in patients with unresectable metastatic colorectal cancer scheduled to undergo placement of a hepatic arterial infusion (HAI) pump was carried out. Thirteen patients were enrolled between November 2003 and September 2006. Dose-limiting veno-occlusive disease was observed at 60 mg/m². At the MTD of 40 mg/m² only minor transient liver dysfunction was observed. Ultrafilterable platinum area under the curve and maximum concentration delivered by IHP increased nonlinearly with dose as did platinum concentrations in liver biopsies obtained at the end of the 60 min IHP. Seventy-seven percent of patients had a >50% decrease in serum carcinoembryonic antigen (CEA) after IHP. The overall response rate to the combined IHP and HAI therapy was 66%. One patient had a durable complete response (>4 years). We conclude that hyperthermic IHP with oxaliplatin was safe and feasible at a dose of 40 mg/m². The ability to obtain complete vascular isolation with open IHP was confirmed. The response rate in this small phase I study was encouraging.

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Title: A Phase I Study of Hyperthermic Isolated Hepatic Perfusion with Oxaliplatin in the Treatment of Unresectable Liver Metastases from Colorectal Cancer
Authors: Herbert J. Zeh III, MD
Charles K. Brown, MD, PhD
Matthew P. Holtzman, MD
Merrill J. Egorin, MD
Julianne L. Holleran, BS
Douglas M. Potter, PhD
David L. Bartlett, MD
Publication date: 01-02-2009
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 2/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-008-0179-5

At a glance: The STEP trials

Springer Medicine

A Phase I Study of Hyperthermic Isolated Hepatic Perfusion with Oxaliplatin in the Treatment of Unresectable Liver Metastases from Colorectal Cancer

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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