Sorafenib and locoregional deep electro‑hyperthermia in advanced hepatocellular carcinoma: A phase II study

Gadaleta‑Caldarola,Gennaro; Infusino,Stefania; Galise,Ida; Ranieri,Girolamo; Vinciarelli,Gianluca; Fazio,Vito; Divella,Rosa; Daniele,Antonella; Filippelli,Gianfranco; Gadaleta,Cosmo  Damiano

doi:10.3892/ol.2014.2376

Sorafenib and locoregional deep electro‑hyperthermia in advanced hepatocellular carcinoma: A phase II study

Authors:
- Gennaro Gadaleta‑Caldarola
- Stefania Infusino
- Ida Galise
- Girolamo Ranieri
- Gianluca Vinciarelli
- Vito Fazio
- Rosa Divella
- Antonella Daniele
- Gianfranco Filippelli
- Cosmo Damiano Gadaleta
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Affiliations: Interventional Radiology and Medical Oncology Unit, National Cancer Research Centre, National Cancer Institute ‘Giovanni Paolo II’, Bari 70124, Italy, Medical Oncology Unit, ‘S. Francesco di Paola’ Hospital, Via Promintesta, Paola 87027, Italy, Apulia Cancer Registry, Statistic and Epidemiology Unit, National Cancer Research Centre, National Cancer Institute ‘Giovanni Paolo II’, Bari 70124, Italy, Clinical Pathology Laboratory, National Cancer Research Centre, National Cancer Institute ‘Giovanni Paolo II’, Bari 70124, Italy, Medical Oncology Unit, ‘S. Francesco di Paola’ Hospital, Via Promintesta, Paola 87027, Italy
Published online on: July 24, 2014 https://doi.org/10.3892/ol.2014.2376
Pages: 1783-1787

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Abstract

The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro‑hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55‑73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression‑free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2‑6.2) and 10.4 (95% CI, 10‑11) months, respectively. The overall incidence of treatment‑related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand‑foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC.

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