Acknowledgments This study was supported by the French Association Vaincre la Mucoviscidose and by the Minist��re de l’Education Nationale, de la Recherche et de la Technologie. We thank C. Baritaud for his technical assistance.
Hepatocellular carcinoma selleck chem (HCC) is a major cause of cancer death and morbidity worldwide (Johnson, 1996) It is frequently complicated by pre-existing chronic liver disease, limiting therapeutic options. While early disease can be managed by resection or local ablation, decreased hepatic reserve may limit the options for surgery or systemic therapy. Furthermore, response rates for systemic therapy are low: no single agent has a response rate higher than approximately 20%, and none improves survival (Leung and Johnson, 2001).

Multiagent therapy using cis-platinum, doxorubicin, 5-fluorouracil, or interferon-alpha may show higher response rates (Leung et al, 1999). However, because patients with HCC frequently have advanced liver disease and associated comorbidities, they are often unable to tolerate intensive and toxic treatment. On the basis that some HCCs have hormone receptors, hormonal approaches (including tamoxifen in a variety of doses) have been evaluated; however, none of these has shown a survival advantage over best supportive care (Chow et al, 2002). A small randomised trial conducted by Kouroumalis et al (1998) suggested that survival was longer in a group treated with short-acting octreotide than in an untreated control group (median survival 13 vs 4 months, 12-month survival 56 vs 13%, P=0.002).

High-affinity somatostatin receptors capable of binding octreotide are present in approximately 40% of HCC, and not in adjacent liver. However, the numbers of high-affinity receptors are lower than reported for neuroendocrine tumours (Reubi et al, 1999). Somatostatin is a potent inhibitor of several growth factors and angioneogenesis (Florio et al, 2003); it also has immune-modulating properties (Lambrecht, 2001). Neuroendocrine and epithelial tumour cell growth can be inhibited in vitro and in vivo by the semisynthetic somatostatin analogue, octreotide (Lamberts et al, 1990). The long-acting depot form of octreotide (sandostatin long-acting release (LAR)) is formulated in microspheres, enabling treatment to be delivered by monthly intramuscular (i.m.) injection.

It is currently used for the treatment of acromegaly (Freda, 2002) and functional neuroendocrine tumours (de Herder and Lamberts, 2002). Little information is available about its elimination kinetics in cirrhosis, although the short-acting form has been studied (Jenkins et al, 1998). In patients with portal hypertension, octreotide has been used extensively in the management of acute variceal bleeding and other complications, Dacomitinib where it reduces portal blood pressure in patients with poor liver function (Jenkins et al, 1997).