Normal and hyperplastic prostate glandular epithelium does not express somatostatin(Drug information on somatostatin) receptors. Neuroendocrine prostatic cells contain bioactive secretory products such as chromogranin A, serotonin, and neuron-specific enolase. The stromal smooth muscle cells around glandular epithelium and ganglion cells of the prostatic plexus are positive for somatostatin subtype 2 receptors (sst 2). In prostate cancer, however, there is nonhomogeneous distribution of sst 1. In the peritumoral veins of prostate cancer, sst 2 receptors were found by Reubi et al in 14 of 27 samples.
Neuroendocrine differentiation is a common feature of prostatic adenocarcinoma, although the prognostic value of neuroendocrine differentiation is controversial. There are scattered clusters of neuroendocrine differentiated cells among the non-neuroendocrine malignant cells. The neuroendocrine differentiation in prostate cancer results in an abnormal phenotype and an incomplete expression of neuroendocrine substances. This phenotypic shift generates cancer cells more adaptable to environmental changes. These cells tend to be androgen-independent rather than androgen-dependent. Elevated chromogranin A and neuron-specific enolase levels in the serum correlate with androgen independence, and distant metastases, but not with locally progressive disease. For prostate carcinoma with neuroendocrine differentiation, the serum markers of the chromogranin family are of more promising prognostic value than neuroendocrine tissue characterization.[5,6]
Octreotide (Sandostatin) is a general inhibitor of neuroendocrine secretion and may inhibit neuroendocrine tumor growth. Imaging in hormone-refractory prostate cancer using somatostatin receptor scintigraphy with 111In-pentetreotide (OctreoScan, Mallinkrodt Imaging) will often be positive at the site of the primary tumor as well as at sites of bone metastases. The presence of somatostatin receptors in tumors, determined using radiolabeled octreotide(Drug information on octreotide) imaging, has prompted clinical trials with octreotide.
In one trial, by Logothetis et al, 20 of 24 patients with hormone-refractory prostate cancer were evaluable for efficacy. Octreotide treatment was administered at a dose of 100 µg subcutaneously three times daily. In this trial, 14 of 20 patients reported subjective improvement in their pain. There was no evidence of objective tumor regression.
More recently, Acosta has treated 18 patients with progressive hormone-refractory prostate cancer using octreotide LAR depot (Sandostatin LAR Depot) at 30 mg/month. Eleven of 18 patients had tumors positive for somatostatin receptors demonstrated by somatostatin receptor scintigraphy. In 9 of 18 patients, there was a greater than 50% decrease in prostate-specific antigen levels. In 8 of 18 patients, there was a 50% reduction in the number of metastases visualized by somatostatin receptor scintigraphy.
In conclusion, there are conflicting clinical results when octreotide has been used for hormone-refractory prostate cancer. Further clinical studies are clearly needed in light of Acosta’s provocative findings. An intriguing question is whether other somatostatin receptors besides the sst 2 receptor may be relevant. When analogs of somatostatin such as SOM 230, which binds to somatostatin receptor subtypes 1, 2, and 3, as well as 5, become clinically available, they deserve evaluation in this challenging disease setting.