title: Phase I study of heat-deployed liposomal doxorubicin during radiofrequency ablation for hepatic malignancies.
abstract: OBJECTIVE
  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.
  
  
  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 concentration-time 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.
authors.affiliation: Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 9000 Rockville Pk., Building 10, Room 1C364, MSC 1182, Bethesda, MD 20892, USA. locklinj@cc.nih.gov
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
authors.forename: Ronnie T
authors.initials: RT
authors.lastname: Poon
authors.forename: Julia K
authors.initials: JK
authors.lastname: Locklin
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Dreher
authors.forename: K K
authors.initials: KK
authors.lastname: Ng
authors.forename: Michelle
authors.initials: M
authors.lastname: Eugeni
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Seidel
authors.forename: Sergio
authors.initials: S
authors.lastname: Dromi
authors.forename: Ziv
authors.initials: Z
authors.lastname: Neeman
authors.forename: Michael
authors.initials: M
authors.lastname: Kolf
authors.forename: Christopher D V
authors.initials: CD
authors.lastname: Black
authors.forename: Raj
authors.initials: R
authors.lastname: Prabhakar
authors.forename: Steven K
authors.initials: SK
authors.lastname: Libutti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D017115:Catheter Ablation / Q000379:methods*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011859:Radiography; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin