TY - JOUR
T1 - Phase i study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies
AU - Wood, Bradford J.
AU - Poon, Ronnie T.
AU - Locklin, Julia K.
AU - Dreher, Matthew R.
AU - Ng, K. K.
AU - Eugeni, Michelle
AU - Seidel, Geoffrey
AU - Dromi, Sergio
AU - Neeman, Ziv
AU - Kolf, Michael
AU - Black, Christopher D.V.
AU - Prabhakar, Raj
AU - Libutti, Steven K.
N1 - Funding Information:
This project has been funded in whole or in part with federal funds from the National Cancer Institute and the Intramural Research Program of the National Institutes of Health (NIH), and is also supported by NIH/Celsion Cooperative Research Development Agreement 01974 and contract no. HHSN261200800001E.
PY - 2012/2
Y1 - 2012/2
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/m2 and 60 mg/m2 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/m2, and the MTD was defined as 50 mg/m2. 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/m2) 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.
AB - 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/m2 and 60 mg/m2 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/m2, and the MTD was defined as 50 mg/m2. 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/m2) 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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U2 - 10.1016/j.jvir.2011.10.018
DO - 10.1016/j.jvir.2011.10.018
M3 - Article
C2 - 22178041
AN - SCOPUS:84856001228
SN - 1051-0443
VL - 23
SP - 248-255.e7
JO - Journal of Vascular and Interventional Radiology
JF - Journal of Vascular and Interventional Radiology
IS - 2
ER -