GH, IGF-I and Somatostatin Analogues in Hepatocellular Carcinoma
Status:
Completed
Trial end date:
2008-12-01
Target enrollment:
Participant gender:
Summary
The hepatocellular carcinoma (HCC) represents more than 5% of all human malignancies, with
more than 500,000 deaths per year (1). In Campania region, mortality for HCC is 2 times
higher than in the rest of Italy because of a higher locally prevalence of hepatitis-C virus
infection.
Development of HCC in liver cirrhosis is associated with increased DNA synthesis and
regeneration of hepatocytes (2). Hepatocyte growth factor, the transforming growth factor-α,
the fibroblast growth factor are well studied (3,4) while the insulin-like growth factor
system (IGF-I, IGF-II and their binding proteins) has been less investigated. IGF-I and
IGF-II modulate growth, metabolism and cell differentiation and have specific receptors in
the liver (5). IGF-I levels in the upper normal range have been associated with an increased
risk to develop prostate cancer (6), breast cancer (7) and colon cancer (8). Some data report
increased expression of IGF-II in HCC (9,10) and others suggest a role of increased IGF-I
bioavailability in HCC (11). We reported increased IGF-I/IGFBP-3 ratio in patients with HCC
compared with those with cirrhosis with a similar liver function, so suggesting increased
IGF-I bioavailability in HCC (12).
There is no currently medical treatment for patients with advanced HCC which has a very poor
prognosis (survival <6 months). Because of limited liver function, classical chemotherapy
cannot be applied (13). In patients with HCC without cirrhosis, surgery is possible only in
5% while in those with cirrhosis first-line treatment is still questioned as survival is <50%
three years after operation. Patients suitable for local resection of HCC are only those with
Child-Pugh's "hyper A" liver function class, who are a minority (14-16). Percutaneous
resection treatments may treat approximately 70%-90% of tumors with maximal diameters of <3
cm (15,17-19).
Somatostatin analogues are indicated in patients with neuroendocrine tumors expressing
somatostatin receptors type 2 and 5 and has excellent safety profile. In advanced HCC, some
studies demonstrated beneficial effects (20,21) while some others did not (22,23).
Only a few data are available on somatostatin receptor expression in HCC (24,25).
Somatostatin analogues have also a clear-cut inhibitory effect on circulating IGF-I levels
with a potential additional effect in delaying HCC progression.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
Federico II University
Collaborators:
Azienda Ospedaliera "D Cotugno" Hospital of Infectious Diseases Ospedali dei Colli