Clinical Research Papers:

Early onset of hypertension and serum electrolyte changes as potential predictive factors of activity in advanced HCC patients treated with sorafenib: results from a retrospective analysis of the HCC-AVR group

Andrea Casadei Gardini _, Emanuela Scarpi, Giorgia Marisi, Francesco Giuseppe Foschi, Gabriele Donati, Emanuela Giampalma, Luca Faloppi, Mario Scartozzi, Nicola Silvestris, Marcello Bisulli, Jody Corbelli, Andrea Gardini, Giuliano La Barba, Luigi Veneroni, Stefano Tamberi, Stefano Cascinu and Giovanni Luca Frassineti

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Oncotarget. 2016; 7:15243-15251. https://doi.org/10.18632/oncotarget.7444

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Andrea Casadei Gardini1, Emanuela Scarpi2, Giorgia Marisi3, Francesco Giuseppe Foschi4, Gabriele Donati5, Emanuela Giampalma6, Luca Faloppi7, Mario Scartozzi8, Nicola Silvestris9, Marcello Bisulli10, Jody Corbelli11, Andrea Gardini12, Giuliano La Barba12, Luigi Veneroni13, Stefano Tamberi8, Stefano Cascinu7, Giovanni Luca Frassineti1

1Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy

2Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola, Italy

3Biosciences Laboratory, IRST IRCCS, Meldola, Italy

4Internal Medicine, Hospital of Faenza, AUSL Romagna, Faenza, Italy

5Internal Medicine, Infermi Hospital, AUSL Romagna, Rimini, Italy

6Radiology Unit, Infermi Hospital, AUSL Romagna, Rimini, Italy

7Department of Medical Oncology, University Hospital of Ancona, Polytechnic University of Marche, Ancona, Italy

8Departments of Medical Oncology, University Hospital Cagliari, Cagliari, Italy

9Medical Oncology Unit, Cancer Institute Giovanni Paolo II, Bari, Italy

10Radiology Unit, Bufalini Hospital, AUSL Romagna, Cesena, Italy

11Unit of Medical Oncology, Hospital of Faenza, AUSL Romagna, Faenza, Italy

12Department of General Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy

13Department of General Surgery, Infermi Hospital, AUSL Romagna, Rimini, Italy

Correspondence to:

Andrea Casadei Gardini, e-mail: [email protected]

Keywords: hepatocellular carcinoma, liver cancer, sorafenib, hypertension, predictive biomarker

Received: October 14, 2015    Accepted: February 09, 2016    Published: February 17, 2016


Hypertension (HTN) is frequently associated with the use of angiogenesis inhibitors targeting the vascular endothelial growth factor pathway and appears to be a generalized effect of this class of agent. We investigated the phenomenon in 61 patients with advanced hepatocellular carcinoma (HCC) receiving sorafenib. Blood pressure and plasma electrolytes were measured on days 1 and 15 of the treatment. Patients with sorafenib-induced HTN had a better outcome than those without HTN (disease control rate: 63.4% vs. 17.2% (p=0.001); progression-free survival 6.0 months (95% CI 3.2-10.1) vs. 2.5 months (95% CI 1.9-2.6) (p<0.001) and overall survival 14.6 months (95% CI9.7-19.0) vs. 3.9 months (95% CI 3.1-8.7) (p=0.003). Sodium levels were generally higher on day 15 than at baseline (+2.38, p<0.0001) in the group of responders (+4.95, p <0.0001) compared to patients who progressed (PD) (+0.28, p=0.607). In contrast, potassium was lower on day 14 (-0.30, p=0.0008) in the responder group (-0.58, p=0.003) than in those with progressive disease (-0.06, p=0.500). The early onset of hypertension is associated with improved clinical outcome in HCC patients treated with sorafenib. Our data are suggestive of an activation of the renin-angiotensin system in patients with advanced disease who developed HTN during sorafenib treatment.

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