Is the efficacy of sorafenib treatment in patients with 5 hepatocellular carcinoma affected by age? Expert Rev. Anticancer Ther. 13(12), 000–000 (2013) Giuseppe Cabibbo*, Marcello Maida, Calogero Camma ` and Antonio Craxı ` Section of Gastroenterology, Di.Bi.Mi.S., University of Palermo, Italy *Author for correspondence: Tel.: +39 091 655 2280 Fax: +39 091 655 2156 g.cab@libero.it 10 Cancer is a prevalent disease in the elderly population and hepatocellular carcinoma (HCC) is a major health problem among all tumors. Curative treatments for early-stage include liver transplantation, resection and percutaneous ablation. Transarterial chemoembolization (TACE) and sorafenib, classified as non-curative treatments, can improve survival for patients with intermediate and advanced tumors, respectively. Even if the incidence of HCC progressively 15 increases with advanced age in all populations, reaching a peak at 70 years, few reports concerning correct management of HCC in elderly patients exist. Moreover, data from large randomized controlled trials (RCT) poorly reflect the elderly population that is often quantitatively and qualitatively underrepresented, as a result of the presence of tight enrolment criteria. The aim of this brief review is to highlight the main concerns, pitfalls and 20 warnings regarding the management of HCC in elderly patients, with particular focus on systemic therapy with sorafenib. 25 KEYWORDS: elderly • hepatocellular carcinoma • safety • sorafenib • treatment Cancer is a prevalent disease in the elderly pop- ulation. Sixty percent of incident cancer cases and 70% of mortality occurs in patients 30 >65 years of age. This, combined with a grow- ing rise in elderly population, will lead in the future to a progressive increase of overall cancer prevalence. Moreover, many elderly individuals can be considered clinically ‘fragile’ or 35 ‘vulnerable’, due to their lifetime accumulation of one or more chronic disease. In fact, beyond chronological age, the presence of comorbidities is associate with a lower use of aggressive cancer treatments, including surgery, chemotherapy 40 and radiation therapy. This conservative approach could be due to reduced remaining life expectancy, to the number and severity of associated diseases and to the assessment of the benefits versus the risks of treatments. 45 Among all cancers, hepatocellular carcinoma (HCC) is a major health problem. It is the sixth most common tumor, and the third most com- mon cause of cancer-related death worldwide [1–3]. It is well known that cirrhosis underlies 50 HCC in most of the patients and the liver functional impairment has a significant impact on prognosis, irrespective of the tumor stage. Moreover, liver function is a key factor to indi- cate those treatments with potential deleterious effects on the liver [4]. Even if the incidence of HCC increases progressively with advanced age in all populations, reaching a peak at 70 years [5], few reports concerning correct management of HCC in elderly patients exist. Moreover, data from RCTs poorly reflect the elderly popula- tion that is often quantitatively and qualitatively underrepresented, as a result of the presence of tight enrollment criteria [6]. The aim of this brief review is to highlight the main concerns, pitfalls and warnings regard- ing the management of HCC in elderly patients, with particular focus on systemic ther- apy with sorafenib. Search strategy Studies for consideration in this article were retrieved from the MEDLINE database using the search terms ‘hepatocellular carcinoma’, ‘liver cancer’ and ‘primary liver cancer’, both www.expert-reviews.com 10.1586/14737140.2013.859989 Ó 2013 Informa UK Ltd ISSN 1473-7140 1 Drug Profile