Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.
Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.
Cebon
J
J
AGITG Trial Coordinating Centre, NHMRC Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown, NSW 1450, Australia. jonathan.cebon@ludwig.edu.au
Findlay
M
M
Hargreaves
C
C
Stockler
M
M
Thompson
P
P
Boyer
M
M
Roberts
S
S
Poon
A
A
Scott
A M
AM
Kalff
V
V
Garas
G
G
Dowling
A
A
Crawford
D
D
Ring
J
J
Basser
R
R
Strickland
A
A
Macdonald
G
G
Green
M
M
Nowak
A
A
Dickman
B
B
Dhillon
H
H
Gebski
V
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D053379:Chromogranin A; D002864:Chromogranins / Q000187:drug effects; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011788:Quality of Life; D017481:Receptors, Somatostatin / Q000096:biosynthesis* / Q000187:drug effects; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D053379:Chromogranin A; D002864:Chromogranins; D003692:Delayed-Action Preparations; D017481:Receptors, Somatostatin; D015282:Octreotide