Hepatocellular carcinoma (HCC) is the third most frequent
cause of cancer death worldwide, causing 549,000 deaths in 200010% of all
cancer deaths. There are strong etiologic associations with hepatitis C,
hepatitis B, alcohol, other causes of cirrhosis, and dietary aflatoxins. The US
incidence of HCC is 2.4/100,000 persons/year and rising due to the increased
prevalence of hepatitis C. After the current cohort of patients infected with
the chronic hepatitis C virus passes, there will likely be a continued increase
in the US incidence of HCC due to increasing rates of obesity-related
nonalcoholic steatohepatitis, which causes many cases of "cryptogenic
Few patients with HCC qualify for curative treatment.
Comparing US Surveillance, Epidemiology, and End Results (SEER) data from the
1987 through 1991 and 1991 through 1996 time periods, only 0.8% of patients in
both time periods underwent curative surgery. Current treatments for
early-stage HCC, representing less than 20% of HCC seen at tertiary centers,
include surgical resection, liver transplantation, and local ablation therapies
including percutaneous ethanol injection or radiofrequency ablation.[2,3] For
more than 80% of patients with advanced-stage HCC, chemotherapy is usually
ineffective because liver dysfunction enhances chemotherapy-induced
hepatotoxicity and portal hypertension with splenomegaly enhances cytopenias.[2,3]
Octreotide (Sandostatin) has antiangiogenic and
antineoplastic properties, and there have been case reports of regression of HCC
in patients treated with octreotide. In 1998, Kouroumalis et al published the
results of a randomized controlled trial of octreotide in advanced HCC.
Patients were randomized to receive no therapy (n = 30) or 250 µg of octreotide
subcutaneously bid (n = 28). The groups were equally matched for the presence of
cirrhosis, gender, bilirubin, albumin, and Child-Pugh class. Octreotide had a
significant effect on patient outcome, with a median survival of 13 months in
the treated group vs 4 months in the untreated group (P = .002).
Adverse effects included mild diarrhea in 40% of patients and
treatment discontinuation in 14% of patients because of the need for
subcutaneous administration twice daily. Fifty-four percent of patients reported
improved overall well-being, 86% reported increased appetite, and 43% had
increased weight gain.
Currently, a number of pilot and advanced-phase studies of
long-acting octreotide LAR depot in advanced HCC are being conducted in Europe
and the United States to assess tumor response. Important objectives of these
studies are to confirm the reported gains in survival and quality of life, to
investigate the relationship of octreotide receptor status to response, and to
determine the optimal dosing of long-acting octreotide LAR depot in patients
with advanced HCC.
1. El-Serag HB, Mason AC, Key C: Trends in survival of
patients with hepatocellular carcinoma between 1977 and 1996 in the United
States. Hepatology 33:62-65, 2001.
2. Aguayo A, Patt YZ: Nonsurgical treatment of hepatocellular
carcinoma. Semin Oncol 28:503-513, 2001.
3. Treiber G: Systemic treatment of hepatocellular carcinoma. Dig Dis 19:311-323, 2001.
4. Kouroumalis EA: Octreotide for cancer of the liver and
biliary tree. Chemotherapy 47(suppl 2):150-161, 2001.
5. Kouroumalis E, Skordilis P, Thermos K, et al: Treatment of
hepatocellular carcinoma with octreotide: A randomised controlled study. Gut
6. Dimitroulopoulos D, Tsamakidis K, Zisimopoulos A, et al:
Efficacy of octreotide acetate long-acting formulation in treating patients with
advanced hepatocellular carcinoma. Gastroenterology 120(suppl 1):A560,