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Various therapeutic approaches for unresectable hepatocellular carcinoma (HCC) have been suggested in recent years. However, major advances concerning tumour regression or patient survival were not achieved. A few trials have assessed the effect of the somatostatin analogue octreotide in advanced HCC with divergent results.1,2 The latter might be due to expression of somatostatin receptor type 2 (SSTR2) in some but not all patients with HCC.3,4 Herein we describe a patient with advanced HCC who was treated with long acting octreotide, which resulted in complete and prolonged regression of the tumour.
The patient was diagnosed with HCC after a suspect nodule was detected in the abdominal ultrasound. Laboratory testing revealed a highly increased alpha fetoprotein (AFP) level and positive hepatitis C virus antibodies. Computed tomography (CT) of the liver displayed multiple tumours (maximum diameter 5 cm) in segment seven and two smaller nodules in segments six and one. Histology of an ultrasound guided biopsy revealed HCC. Due to the advanced stage of the tumour, surgical resection was not feasible. As the patient refused local ablative therapies, treatment with octreotide was initiated (initially 250 μg twice daily followed by long acting octreotide (Sandostatin LAR) 10 mg monthly). Four months later a 50–70% reduction in the size of the multifocal tumours was demonstrated by CT. Furthermore, complete regression of the formerly described tumours was noted 10 months after initiation of octreotide therapy. This was paralleled by normalisation of the formerly elevated AFP values (33.1 ng/ml v 7615.3 ng/ml). Octreotide receptor scintigraphy performed after 12 months and 19 months of therapy did not reveal any suspicious enhancement. However, after 13 and 19 months a gradual increase in AFP levels from 37 to 223 ng/ml and a new suspicious liver nodule by CT scan was observed. To date, the patient has not experienced any tumour associated symptoms or drug related side effects and has been in excellent condition during the 22 months of treatment.
The survival improving treatment effects of octreotide described by Kouroumalis and colleagues1 were not confirmed in a subsequent randomised placebo controlled trial.2 Of the octreotide receptors expressed in the liver, octreotide has the highest affinity for SSTR2 compared with the four other isoforms of the somatostatin receptors.3 SSTR2 is expressed in HCC3,4 and has been shown to play a major role in mediating cell cycle arrest.5 Although we were not able to prove SSTR expression in our patient due to tissue preparation in another hospital, high SSTR2 expression in our patient might be the reason for the unusual beneficial clinical course. The recent increase in AFP levels could reflect the ability of the tumour cells to escape somatostatin receptor treatment, possibly by downregulation or mutation of the respective receptor.
To the best of our knowledge, complete and prolonged regression of advanced HCC with normalised AFP levels during octreotide treatment has not been described previously. Based on our observation and the divergent results of recent studies, forthcoming trials evaluating the effect of octreotide in advanced HCC might additionally stratify patients according to the respective somatostatin receptor expression profile of tumour cells.
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