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Long-Acting Octreotide LAR Depot in the Treatment of Advanced Hepatocellular Carcinoma

Long-Acting Octreotide LAR Depot in the Treatment of Advanced Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer death worldwide, causing 549,000 deaths in 2000—10% 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.[1] 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 cirrhosis."

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.[1] 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.[4] In 1998, Kouroumalis et al published the results of a randomized controlled trial of octreotide in advanced HCC.[5] 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).[5]

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.[5]

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.[6] 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.

References

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 42:442-447, 1998.

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, 2001.

 
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