Normal and hyperplastic prostate glandular epithelium does
not express 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
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
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
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