Patients with Cushing’s disease experienced declines in
cortisol levels when treated with the novel somatostatin analogue pasireotide,
according to results of a double blind, phase 3 study.
of patients had a significant reduction in cortisol secretion with improvement
in the clinical features of Cushing’s syndrome; however, only 25% of patients
had normalization of cortisol,” James
W. Findling, MD, FACP, of
the division of endocrinology,
metabolism and clinical nutrition at the Medical College of Wisconsin, told Endocrine Today. “The most surprising finding was
that many patients (73%) had increases in glucose levels. Since diabetes
mellitus complicates the course of many patients with Cushing’s disease, this
problem will need to be addressed proactively.”
Pasireotide (SOM230, Novartis) is a potential therapy for
Cushing’s disease that has been shown to have a unique, broad
somatostatin-receptor–binding profile, with high binding affinity for
somatostatin-receptor subtype 5.
colleagues randomly assigned 162 patients with Cushing’s disease who had a
urinary free cortisol level of at least 1.5 times the upper limit of the normal
range to receive subcutaneous pasireotide at a dose of 600 mcg (n=82 patients)
or 900 mcg (n=80 patients) twice a day.
Those patients who
had a urinary free cortisol that did not exceed two times the upper limit of the
normal range and did not exceed the baseline level at 3 months continued to
receive their randomly assigned dose; the rest received an additional 300 mcg
twice a day.
baseline, 78% of patients had moderate-to-very severe hypercortisolism.
Of the patients who
received 600 mcg of pasireotide, 12 had a normalized urinary free cortisol
level (the primary endpoint) compared with 21 of those in the 900-mcg group.
Furthermore, the median urinary free cortisol level decreased by almost half by
the second month of treatment and remained stable in both groups.
adverse events were common in patients treated with pasireotide; other adverse
events were similar to those associated with other somatostatin analogues.
by the FDA, pasireotide should be considered in patients with persistent or
recurrent hypercortisolism after pituitary surgery and/or radiotherapy for
Cushing’s disease,” Findling said. “The effectiveness of therapy should be apparent
within a short time (3 to 4 months), and careful attention to glucose levels
during treatment will be essential.”
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Disclosure: Research was supported by Novartis Pharma. Dr. Findling and several of
the other researchers report receiving consulting fees and/or support from