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Experimental and clinical studies with somatostatin analogue octreotide in small cell lung cancer
V M Macaulay1, I E Smith, M J Everard
1Lung Unit, Royal Marsden Hospital, Sutton, Surrey, UK.
Abstract:
We have detected somatostatin receptors (SSR) by autoradiography in 3/4 established small cell lung cancer (SCLC) cell lines but not in two non-SCLC cell lines. The growth of 1/3 SSR positive SCLC cell lines was significantly inhibited by the long-acting somatostatin analogue octreotide (SMS 201-995, Sandostatin) 10(-9) M. We treated 20 SCLC patients with octreotide 250 micrograms three times daily for 1 week prechemotherapy (six patients) or at relapse after chemotherapy (14). Octreotide was well tolerated, and serum insulin-like growth factor-I levels were suppressed to 62 +/- 7% of pre-treatment levels. However there was no evidence of anti-tumour activity measured by tumour bulk or serum levels of neuron-specific enolase. In one patient metastatic skin nodules were shown to be SSR positive before and at the end of 2 weeks octreotide. Despite this the patient had progressive disease, and tumour cells obtained by fine needle aspirate before and after treatment showed no growth inhibition when cultured with octreotide immediately or following establishment as a cell line. In summary we saw little correlation between SSR expression and growth inhibition by octreotide, either in vitro or clinically.
Insights
Somatostatin receptors (SSR) were detected in small cell lung cancer (SCLC) cell lines. However, the somatostatin analogue octreotide showed limited efficacy in inhibiting SCLC growth, both in vitro and clinically.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Small cell lung cancer (SCLC) is an aggressive form of lung cancer.
- Somatostatin receptors (SSR) are implicated in various cellular functions and cancer growth.
- Octreotide is a long-acting somatostatin analogue with potential therapeutic applications.
Purpose of the Study:
- To investigate the presence of somatostatin receptors (SSR) in small cell lung cancer (SCLC) cell lines.
- To evaluate the efficacy of octreotide in inhibiting the growth of SSR-positive SCLC cells in vitro and in patients.
Main Methods:
- Autoradiography was used to detect SSR in SCLC and non-SCLC cell lines.
- In vitro studies assessed the effect of octreotide on SCLC cell line growth.
- A clinical trial treated SCLC patients with octreotide before chemotherapy or at relapse.
Main Results:
- SSR were detected in 3/4 SCLC cell lines but not in non-SCLC lines.
- Octreotide significantly inhibited the growth of only 1/3 SSR-positive SCLC cell lines in vitro.
- Clinical treatment with octreotide was well-tolerated, suppressed IGF-I levels, but showed no significant anti-tumour activity.
Conclusions:
- There is a limited correlation between SSR expression and octreotide's growth inhibitory effects in SCLC.
- Octreotide demonstrates poor clinical efficacy for SCLC despite SSR presence.
- Further research is needed to explore targeted therapies for SCLC.