A randomized placebo-controlled study of long-acting octreotide for the treatment of advanced hepatocellular carcinoma

Abstract

Although various types of treatment of hepatocellular carcinoma (HCC) have been tried, the prognosis remains dismal, especially in patients with advanced stage of the disease. Somatostatin analogues exert antitumor effects. HCC have been shown to exhibit somatostatin receptors. The present randomized placebo-controlled study aimed at examining the efficacy of long-acting octreotide (Sandostatin LAR) for the treatment of advanced HCC. Seventy patients were randomized to receive a 2-week course of 250 g short-acting octreotide twice daily followed by Sandostatin LAR 30 mg injection once every 4 weeks for 6 doses (n ‫؍‬ 35) or placebo (control group) (n ‫؍‬ 35). The clinical and laboratory parameters were monitored. There was no difference in the cumulative survival between the Sandostatin LAR-treated group compared with the control group [median survival 1.93 months vs. 1.97 months, respectively, P ‫؍‬ NS (log-rank test)]. There was no tumor regression and no reduction of ␣-fetoprotein (AFP) levels in patients receiving Sandostatin LAR treatment. There was no improvement of quality of life assessed by Karnofsky performance score. In conclusion, Sandostatin LAR monotherapy did not have survival benefit in our selected group of patients with advanced HCC. Further studies should be performed in patients with less advanced disease and/or different etiology to evaluate its benefit. (HEPATOLOGY 2002;36:687-691.) H epatocellular carcinoma (HCC) is responsible for nearly a quarter of a million deaths per year in the world. 1 It is of particular importance in endemic areas such as Asia where there is a high prevalence of chronic hepatitis B virus (HBV) infection. Although a screening program increases the chance of receiving more curative treatment, 2,3 many patients still present at a relatively late stage with advanced disease.Surgical resection is the first choice of treatment in patients without portal vein involvement and distant metastasis. However, it requires a relatively good liver function reserve. 4 Only less than 30% of patients are eligible for resection because of the high prevalence of underlying cirrhosis secondary to HBV infection. 2 For patients with unresectable HCC, there are few options. Transcatheter arterial chemoembolization (TACE) requires a reasonable liver reserve because of the risk of hepatic decompensation after TACE. 5,6 Liver transplantation, another option for small HCC with poor liver reserve, is limited by the scarcity of organ donation. Other modalities of treatment include percutaneous alcohol injection, which is only applicable for tumors less than 3 cm. 7 Thermal ablation for small tumors using heating effect by radiofrequency or microwave has also been tried. 8 These local ablative therapies are not suitable for patients with large HCC or advanced HCC with portal vein thrombosis with or without distant metastasis. Despite the extensive efforts in exploring the treatment of HCC, the prognosis remains dismal. The prognosis is even worse in patients with advanced unresectable HCC and...

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

“…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).…”

“…However, a treatment that benefits only a subset of patients may still be clinically worthwhile. The very different outcomes in the randomised trials by Kouroumalis and Yuen probably reflect differences in patient selection (Kouroumalis et al, 1998;Yuen et al, 2002). The Yuen study had subjects with more advanced disease, a higher proportion with viral hepatitis, and a median survival of only 2 months.…”

Current management strategy of hepatocellular carcinoma

“…Unfortunately, no single agent or combination of agents given systemically leads to reproducible response rates that show beneficial effect of systemic chemotherapy on survival rates [78] . Tamoxifen, octreotide, interferon, and interleukin-2 have not been shown to be effective in treating HCC in randomized controlled clinical trials [79,80] . The increasing knowledge in the molecular structure of HCC as well as the introduction of molecular targeted therapies in oncology have created an encouraging trend in the management of this disease [81] .…”

New aspects of diagnosis and therapy of hepatocellular carcinoma

“…Systemic chemotherapy with different agents is marginally effective against HCC but severely toxic and unassociated with increased survival Bruix and Sherman, 2005). Agents such as tamoxifen , antiandrogens (Grimaldi et al, 1998) and octreotide (Yuen et al, 2002) are completely ineffective.…”