Search

Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) since 2007 and numerous studies have investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC.

Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012. Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events.

// Andrea Casadei Gardini 1 , Emanuela Scarpi 2 , Luca Faloppi 3, 4 , Mario Scartozzi 4 , Nicola Silvestris 5 , Daniele Santini 6 , Giorgio de Stefano 7 , Giorgia Marisi 8 , Francesca V. Negri 9 , Francesco Giuseppe Foschi 10 , Martina Valgiusti 1 , Giorgio Ercolani 11, 12 , 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 Department of Medical Oncology, Ospedale Generale Provinciale di Macerata ASUR Marche AV3, Macerata, Italy 4 Department of Medical Oncology, University Hospital Cagliari, Cagliari, Italy 5 Medical Oncology Unit, Cancer Institute “Giovanni Paolo II”, Bari, Italy 6 Medical Oncology Department, University Campus Bio-Medico, Via Alvaro del Portillo, Rome, Italy 7 Infectious Diseases and Interventional Ultrasound Unit, D. Cotugno Hospital, Naples, Italy 8 Biosciences Laboratory, IRST IRCCS, Meldola, Italy 9 Medical Oncology Unit, University Hospital, Parma, Italy 10 DPT Internal Medicine, Faenza Hospital, Faenza, AUSL Romagna, Forli, Italy 11 Department of General Surgery, Morgagni-Pierantoni Hospiatal, AUSL Romagna, Forli, Italy 12 Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy Correspondence to: Andrea Casadei Gardini, email: andrea.casadei@irst.emr.it Keywords: systemic immune-inflammation index, inflammation, biomarker, hepatocellular carcinoma, neutrophil-to-lymphocyte ratio Received: June 21, 2016 Accepted: August 15, 2016 Published: August 24, 2016 ABSTRACT We evalueted a systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) with the aim to explored their prognostic value in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. 56 advanced HCC patients receiving sorafenib were available for our analysis. Lymphocyte, neutrophil and platelet were measured before beginning of treatment and after one month. Patient with SII ≥ 360 showed lower median PFS (2.6 vs. 3.9 months, P < 0.026) and OS (5.6 vs. 13.9 months, P = 0.027) with respect to patients with SII < 360. NLR ≥ 3 had a lower median PFS (2.6 vs. 3.3 months, P < 0.049) but not OS (5.6 vs. 13.9 months, P = 0.062) than those with NLR < 3. After adjusting for clinical covariates SII and NLR remained an independent prognostic factor for OS. The SII and NLR represent potential prognostic indicator in patients with advanced HCC treated with sorafenib.