Treatment of hepatocellular cancer with the long acting somatostatin analog lanreotide in vitro and in vivo.

Raderer, Markus; Hejna, Michael; Müller, Christian; Kornek, Gabriela; Kurtaran, Amir; Virgolini, Irene; Fiebieger, W.; Hamilton, Gerhard; Scheithauer, Werner

doi:10.3892/ijo.16.6.1197

Cited by 47 publications

(58 citation statements)

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“…Octreotide was previously used in HCC patients with conflicting results (14)(15)(16)(17)(18)(19)(20)(21). We showed, in a previous study, that combination of octreotide and radiofrequency ablation 6 produced about 80.0% of disease control and interesting mean overall survival (31.4 months) in a series of advanced HCC patients (22).…”

Section: Introductionmentioning

confidence: 99%

Sorafenib plus octreotide is an effective and safe treatment in advanced hepatocellular carcinoma: multicenter phase II So.LAR. study

Prete

Montella

Caraglia

et al. 2009

Cancer Chemother Pharmacol

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All patients were assessable for safety and efficacy. Sixteen patients out of 50 (34%) were naïve from other therapies, while all the others were previously treated with local and/or systemic treatments. We achieved 5 partial responses (10%), 33 stable diseases (66%) and 12 progressions of disease (24%). Median time to progression was 7.0 months (95% CI, 3.0 to 10.9 months) and median overall survival was 12 months (95% CI, 6.3 to 17.4 months). Treatment was well tolerated. Diarrhoea (6%) and hypertension (4%) were the most frequent grade 3 toxicities. Conclusions. Our data suggest that the combination between sorafenib and long acting octreotide is active and well tolerated in patients with advanced HCC and could represent another efficacious chance for the management of this population.4

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Section: Introductionmentioning

confidence: 99%

Sorafenib plus octreotide is an effective and safe treatment in advanced hepatocellular carcinoma: multicenter phase II So.LAR. study

Prete

Montella

Caraglia

et al. 2009

Cancer Chemother Pharmacol

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“…(16) Somatostatin analogs also exert indirect antitumor activity mainly by inhibiting tumoral neo-angiogenesis (17) and inhibition of growth factor release. They have shown antitumoral effects in liver cancer cell lines in vitro (18)(19)(20)(21) and in in vivo animal models (22) but showed conflicting results in clinical trials on humans with advanced cancer. (23)(24)(25)(26)(27) Lanreotide has not been tested in a prophylactic setting.…”

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confidence: 99%

Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide

et al. 2007

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Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death, and its incidence is increasing worldwide. Due to the known risk factors (mainly hepatitis B and C viruses), we believe there is a rationale for a chemopreventive approach to treat HCC. Here, based on described in vitro data, we evaluated the preventive effects of lanreotide, a somatostatin analog, on the induction of early carcinogenic events. We monitored preneoplastic foci induced by a two-stage initiation/promotion model of hepatocarcinogenesis in male Wistar rats, using diethylnitrosamine and 2-acetylaminofluorene. Lanreotide was given starting the day after the first diethylnitrosamine injection. By quantitative morphometry, we showed that lanreotide significantly decreases the size of induced preneoplastic foci. Analysis of proliferation and apoptosis assessed by immunohistochemistry, showed decreased proliferation and increased cell death in rats treated with lanreotide. As these events were associated with a significant decreased expression of the cell cycle regulator cyclin D1 and an increased expression of the cyclin-dependent kinase inhibitor p27 kip1 compared to the non-treated group, it is tempting to speculate that these factors are involved in the favorable effect of lanreotide. In conclusion, lanreotide significantly decreases early carcinogenic transformation in a two-step rat model. As lanreotide has a low toxicity profile, we believe it would be interesting to evaluate its effect in chemoprevention of HCC. (Cancer Sci 2007; 98: 1831-1839) H CC represents a major public health problem. Its incidence is in constant progression, with 2-5 new cases per 100 000 inhabitants/year in western countries and more than 20 per 100 000 inhabitants/year in Asia.(1,2) Curative treatment can only be proposed in 10-20% of cases.The main risk factors of HCC development are cirrhosis and hepatitis B and C that induce genetic alterations leading to preneoplastic, then neoplastic changes. The persistence of infection and/or cirrhosis often leads to tumoral relapse after surgical resection, observed in approximately 20% per year. Therefore, chemoprevention could play an important role in the therapeutic strategy of this disease.In experimental carcinogenesis, preneoplastic foci of altered hepatocytes emerge weeks or months before the appearance of hepatocellular adenomas and HCC.(3) Similar progression has been described in human hepatocarcinogenesis.(4) This fact has led to the development of a number of in vivo systems to study early neoplasia in rat liver.(5) The initiation-promotion or two-stage model of cancer development mimics the early events of the latent period of human carcinogenesis. The initiation stage of cancer development can be produced in rat liver by injection of DEN, (6) a carcinogen that causes DNA ethylation and mutagenesis.(7) Furthermore, DEN has been shown to induce tumors in rodents that closely mimic a subclass of human HCC. Somatostatin analogs (octreotide and lanreotide) are molecules that are widely...

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“…It is impossible to tell from this trial whether this effect on survival was real, and if so, whether it was due to anticancer effects or other effects such as reduction in portal pressure. Subsequent studies with long-acting octreotide analogues have shown less benefit (Raderer et al, 2000;Samonakis et al, 2002) or no benefit (Yuen et al, 2002). In a recent study, patients selected for treatment on the basis of scan positivity were treated with octreotide and, when compared with a control population in a nonrandomised manner, had better outcomes in terms of survival and quality of life (Dimitroulopoulos et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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

Cebon

2006

Br J Cancer

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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.

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Treatment of hepatocellular cancer with the long acting somatostatin analog lanreotide in vitro and in vivo.

Cited by 47 publications

References 0 publications

Sorafenib plus octreotide is an effective and safe treatment in advanced hepatocellular carcinoma: multicenter phase II So.LAR. study

Sorafenib plus octreotide is an effective and safe treatment in advanced hepatocellular carcinoma: multicenter phase II So.LAR. study

Inhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide

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

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