title: 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.
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.
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Casadei Gardini
authors.affiliation: Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.affiliation: Biosciences Laboratory, IRST IRCCS, Meldola, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Marisi
authors.affiliation: Internal Medicine, Hospital of Faenza, AUSL Romagna, Faenza, Italy.
authors.forename: Francesco Giuseppe
authors.initials: FG
authors.lastname: Foschi
authors.affiliation: Internal Medicine, Infermi Hospital, AUSL Romagna, Rimini, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Donati
authors.affiliation: Radiology Unit, Infermi Hospital, AUSL Romagna, Rimini, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Giampalma
authors.affiliation: Department of Medical Oncology, University Hospital of Ancona, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Faloppi
authors.affiliation: Departments of Medical Oncology, University Hospital Cagliari, Cagliari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.affiliation: Medical Oncology Unit, Cancer Institute Giovanni Paolo II, Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Silvestris
authors.affiliation: Radiology Unit, Bufalini Hospital, AUSL Romagna, Cesena, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Bisulli
authors.affiliation: Unit of Medical Oncology, Hospital of Faenza, AUSL Romagna, Faenza, Italy.
authors.forename: Jody
authors.initials: J
authors.lastname: Corbelli
authors.affiliation: Department of General Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gardini
authors.affiliation: Department of General Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: La Barba
authors.affiliation: Department of General Surgery, Infermi Hospital, AUSL Romagna, Rimini, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Veneroni
authors.affiliation: Departments of Medical Oncology, University Hospital Cagliari, Cagliari, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tamberi
authors.affiliation: Department of Medical Oncology, University Hospital of Ancona, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Frassineti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D004573:Electrolytes / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000150:complications*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000009:adverse effects*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects; D012189:Retrospective Studies; D000077157:Sorafenib; D015996:Survival Rate
chemical_list: D004573:Electrolytes; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: hepatocellular carcinoma; hypertension; liver cancer; predictive biomarker; sorafenib