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Abstract Details
Phase III HEAT Study Adding Lyso-Thermosensitive Liposomal Doxorubicin to Radiofrequency Ablation in Patients With Unresectable Hepatocellular Carcinoma Lesions
Tak WY1, Lin SM2, Wang Y3, Zheng J4, Vecchione A5, Park SY6, Chen MH7, Wong S8, Xu R9, Peng CY10, Chiou YY11, Huang GT12, Cai J13, Abdullah BJ14, Lee JS15, Lee JY16, Choi JY17, Gopez-Cervantes J18, Sherman M19, Finn RS20, Omata M21, O'Neal M22, Makris L23, Borys N24, Poon R25, Lencioni R26. Clin Cancer Res. 2017 Oct 10. pii: clincanres.2433.2016. doi: 10.1158/1078-0432.CCR-16-2433. [Epub ahead of print]
Author information
1
Department of Internal Medicine, Liver Research Institute, Kyungpook National University School of Medicine wytak@knu.ac.kr.
2
Liver Cancer Research Center, Chang Gung Memorial Hospital.
3
Third Central Hospital of Tianjin.
4
Department of Medicine, Beijing You An Hospital, Capital Medical University.
5
5National Cancer Institute of Naples.
6
Internal Medicine, Kyungpook National University School of Medicine.
7
Department of Ultrasound, Peking University Cancer Hospital.
8
Chinese General Hospital.
9
Department of Hepatobiliary and Pancreatic Internal Medicine, Hunan Cancer Hospital.
10
Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital.
11
Taipei Veterans General Hospital.
12
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine.
13
Dept. of Abdominal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences.
14
Biomedical Imaging, University of Malaya.
15
Internal Medicine, Inje University Ilsan Paik Hospital.
16
Seoul National University Hospital.
17
Internal Medicine, Kangnam St. Mary's Hospital.
18
St. Luke's Medical Center.
19
Medicine, University of Toronto.
20
Department of Hematology- Oncology, University of California, Los Angeles.
21
Yamanashi Prefectural Central Hospital.
22
BioClinica Inc.
23
Stathmi.
24
Celsion Corporation, Celsion Corporation.
25
Queen Mary Hospital, University of Hong Kong.
26
Interventional Radiology, University of Miami Miller School of Medicine.
Abstract
PURPOSE:
Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to >=40ºC, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax) of 3 to 7 cm.
PATIENTS AND METHODS:
The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA +/- LTLD. The 701 enrolled patients had to have <=4 unresectable HCC lesions, at least 1 of which had a dmax of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy.
RESULTS:
The primary endpoint was not met; in intention-to-treat analysis, the PFS hazard ratio (HR) of RFA + LTLD vs RFA alone was 0.96 (95% confidence interval [CI]: 0.79-1.18; P=0.71) and the OS HR ratio was 0.95 (95% CI: 0.76-1.20; P=0.67). Among 285 patients with a solitary HCC lesion who received >=45 minutes RFA dwell time, the OS HR was 0.63 (95% CI: 0.41-0.96; P<0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin.
CONCLUSION:
Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion >=45 minutes.