Pasireotide for the treatment of Cushing's disease.
BACKGROUND
It is important to treat patients with Cushing's disease as rapidly as possible to limit both the mortality and morbidity of the disease. Pituitary surgery remains the treatment of choice, but the rate of cure at long-term follow-up is suboptimal and recurrence rates are high. If surgery fails or relapse occurs, no treatment has proven to be fully satisfactory. Currently available medical therapies are considered a transient and palliative treatment. However, recently there has been renewed interest in medical therapy due to new insights in pathogenetic mechanisms of corticotroph pituitary tumors.


METHODS
We summarize the pharmacodynamics and possible mechanism of action of pasireotide (SOM230), a novel multireceptor-targeted somatostatin analogue. Pasireotide has a unique binding profile, with high affinity for four of the five somatostatin receptors, especially SSTR(5), the receptor most prevalent in corticotroph tumors.


RESULTS
The reader should gain an understanding of preclinical and clinical data supporting the potential use of pasireotide in patients with Cushing's disease.


CONCLUSIONS
Preliminary data suggest that pasireotide shows promise as a tumor-targeted medical therapy in patients with Cushing's disease. If the efficacy of pasireotide is confirmed by larger studies, this compound may be a useful treatment option not only in patients with severe Cushing's disease, but also in patients with mild hypercortisolism where its efficacy might be more evident.
Clinica di Endocrinologia, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Ancona, Italy. m.boscaro@univpm.it
Giorgio
G
Arnaldi
Marco
M
Boscaro
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D017326:Clinical Trials, Phase III as Topic; D003480:Cushing Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D011485:Protein Binding; D017481:Receptors, Somatostatin / Q000819:agonists*; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D017481:Receptors, Somatostatin; D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; C517782:pasireotide