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 1 , Emanuela Scarpi 2 , Giorgia Marisi 3 , Francesco Giuseppe Foschi 4 , Gabriele Donati 5 , Emanuela Giampalma 6 , Luca Faloppi 7 , Mario Scartozzi 8 , Nicola Silvestris 9 , Marcello Bisulli 10 , Jody Corbelli 11 , Andrea Gardini 12 , Giuliano La Barba 12 , Luigi Veneroni 13 , Stefano Tamberi 8 , Stefano Cascinu 7 , Giovanni Luca Frassineti 1 1 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy 2 Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola, Italy 3 Biosciences Laboratory, IRST IRCCS, Meldola, Italy 4 Internal Medicine, Hospital of Faenza, AUSL Romagna, Faenza, Italy 5 Internal Medicine, Infermi Hospital, AUSL Romagna, Rimini, Italy 6 Radiology Unit, Infermi Hospital, AUSL Romagna, Rimini, Italy 7 Department of Medical Oncology, University Hospital of Ancona, Polytechnic University of Marche, Ancona, Italy 8 Departments of Medical Oncology, University Hospital Cagliari, Cagliari, Italy 9 Medical Oncology Unit, Cancer Institute Giovanni Paolo II, Bari, Italy 10 Radiology Unit, Bufalini Hospital, AUSL Romagna, Cesena, Italy 11 Unit of Medical Oncology, Hospital of Faenza, AUSL Romagna, Faenza, Italy 12 Department of General Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forli, Italy 13 Department of General Surgery, Infermi Hospital, AUSL Romagna, Rimini, Italy Correspondence to: Andrea Casadei Gardini, e-mail: andrea.casadei@irst.emr.it Keywords: hepatocellular carcinoma, liver cancer, sorafenib, hypertension, predictive biomarker Received: October 14, 2015     Accepted: February 09, 2016     Published: February 17, 2016 ABSTRACT 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.