Phase i study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies

Bradford J. Wood, Ronnie T. Poon, Julia K. Locklin, Matthew R. Dreher, K. K. Ng, Michelle Eugeni, Geoffrey Seidel, Sergio Dromi, Ziv Neeman, Michael Kolf, Christopher D V Black, Raj Prabhakar, Steven K. Libutti

Research output: Contribution to journalArticle

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Abstract

Purpose: A phase I dose escalation study was performed with systemically delivered lyso-thermosensitive liposomal doxorubicin (LTLD). The primary objectives were to determine the safe maximum tolerated dose (MTD), pharmacokinetic properties, and dose-limiting toxicity (DLT) of LTLD during this combination therapy. Materials and Methods: Subjects eligible for percutaneous or surgical radiofrequency (RF) ablation with primary (n = 9) or metastatic (n = 15) tumors of the liver, with four or fewer lesions as large as 7 cm in diameter, were included. RF ablation was initiated 15 minutes after starting a 30-minute intravenous LTLD infusion. Dose levels between 20 mg/m 2 and 60 mg/m 2 were evaluated. Magnetic resonance imaging, positron emission tomography, and computed tomography were performed at predetermined intervals before and after treatment until evidence of recurrence was seen, administration of additional antitumor treatment was performed, or a total of 3 years had elapsed. Results: DLT criteria were met at 60 mg/m 2, and the MTD was defined as 50 mg/m 2. RF ablation was performed during the peak of the plasma concentrationtime curve in an effort to yield maximal drug deposition. LTLD produced reversible, dose-dependent neutropenia and leukopenia. Conclusions: LTLD can be safely administered systemically at the MTD (50 mg/m 2) in combination with RF ablation, with limited and manageable toxicity. Further evaluation of this agent combined with RF ablation is warranted to determine its role in the management of liver tumors.

Original languageEnglish (US)
Pages (from-to)248-255
Number of pages8
JournalJournal of Vascular and Interventional Radiology
Volume23
Issue number2
DOIs
StatePublished - Feb 2012
Externally publishedYes

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Hot Temperature
Maximum Tolerated Dose
Liver
Neoplasms
Leukopenia
Neutropenia
Pharmacokinetics
Magnetic Resonance Imaging
liposomal doxorubicin
Recurrence
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Phase i study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies. / Wood, Bradford J.; Poon, Ronnie T.; Locklin, Julia K.; Dreher, Matthew R.; Ng, K. K.; Eugeni, Michelle; Seidel, Geoffrey; Dromi, Sergio; Neeman, Ziv; Kolf, Michael; Black, Christopher D V; Prabhakar, Raj; Libutti, Steven K.

In: Journal of Vascular and Interventional Radiology, Vol. 23, No. 2, 02.2012, p. 248-255.

Research output: Contribution to journalArticle

Wood, BJ, Poon, RT, Locklin, JK, Dreher, MR, Ng, KK, Eugeni, M, Seidel, G, Dromi, S, Neeman, Z, Kolf, M, Black, CDV, Prabhakar, R & Libutti, SK 2012, 'Phase i study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies', Journal of Vascular and Interventional Radiology, vol. 23, no. 2, pp. 248-255. https://doi.org/10.1016/j.jvir.2011.10.018
Wood, Bradford J. ; Poon, Ronnie T. ; Locklin, Julia K. ; Dreher, Matthew R. ; Ng, K. K. ; Eugeni, Michelle ; Seidel, Geoffrey ; Dromi, Sergio ; Neeman, Ziv ; Kolf, Michael ; Black, Christopher D V ; Prabhakar, Raj ; Libutti, Steven K. / Phase i study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies. In: Journal of Vascular and Interventional Radiology. 2012 ; Vol. 23, No. 2. pp. 248-255.
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AU - Poon, Ronnie T.

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AU - Ng, K. K.

AU - Eugeni, Michelle

AU - Seidel, Geoffrey

AU - Dromi, Sergio

AU - Neeman, Ziv

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AU - Black, Christopher D V

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AU - Libutti, Steven K.

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N2 - Purpose: A phase I dose escalation study was performed with systemically delivered lyso-thermosensitive liposomal doxorubicin (LTLD). The primary objectives were to determine the safe maximum tolerated dose (MTD), pharmacokinetic properties, and dose-limiting toxicity (DLT) of LTLD during this combination therapy. Materials and Methods: Subjects eligible for percutaneous or surgical radiofrequency (RF) ablation with primary (n = 9) or metastatic (n = 15) tumors of the liver, with four or fewer lesions as large as 7 cm in diameter, were included. RF ablation was initiated 15 minutes after starting a 30-minute intravenous LTLD infusion. Dose levels between 20 mg/m 2 and 60 mg/m 2 were evaluated. Magnetic resonance imaging, positron emission tomography, and computed tomography were performed at predetermined intervals before and after treatment until evidence of recurrence was seen, administration of additional antitumor treatment was performed, or a total of 3 years had elapsed. Results: DLT criteria were met at 60 mg/m 2, and the MTD was defined as 50 mg/m 2. RF ablation was performed during the peak of the plasma concentrationtime curve in an effort to yield maximal drug deposition. LTLD produced reversible, dose-dependent neutropenia and leukopenia. Conclusions: LTLD can be safely administered systemically at the MTD (50 mg/m 2) in combination with RF ablation, with limited and manageable toxicity. Further evaluation of this agent combined with RF ablation is warranted to determine its role in the management of liver tumors.

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