Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide

Abstract

Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28 -81 years), male 81%, Child -Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0 -9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.

Hepatocellular carcinoma: Exploring the impact of ethnicity on molecular biology

“…The rate of octreotide scan positivity has not been studied in Asian population, while in the Western population it seems to be between 35 and 56% (Nguyen-Khac et al, 2009;Cebon et al, 2006), matching with the rate of positivity in the immunohistochemistry studies.…”

Somatostatin analogues in advanced hepatocellular carcinoma: An updated systematic review and meta-analysis of randomized controlled trials

“…Cebon et al [34] reported that 41% of the HCC tissue samples overexpressed SSTR with high affinity for octreotide. Further studies found high detection rates of SSTR 2, 3 and 5 in HCC cells, although with high heterogenicity even in the same tumor.…”

Impact of different anticancer regimens on biomarkers of angiogenesis in patients with advanced hepatocellular cancer

“…For the long-acting somatostatin analogue octreotide, which revealed conXicting clinical results (Kouroumalis et al 1998;Dimitroulopoulos et al 2002Dimitroulopoulos et al , 2007Raderer et al 2000;Yuen et al 2002;Verset et al 2007;Treiber et al 2007;Becker et al 2007;Cebon et al 2006;Plentz et al 2005;Slijkhuis et al 2005;Rabe et al 2002;Pan et al 2003;Samonakis et al 2002), we and others demonstrated that clinical response was associated with a reduction in systemic vascular endothelial growth factor (VEGF)-A secretion (Treiber et al 2006;Jia et al 2003;Poon et al 2004Poon et al , 2001. Sorafenib, a combined small molecule VEGF/ RAF kinase inhibitor resulted in a moderate prolongation of survival in Child A patients (Abou-Alfa et al 2006;Llovet et al 2007).…”