Sabrina Chiloiro1, Chiara Bima1, Tommaso Tartaglione2,3, Antonella Giampietro1, Marco Gessi4, Liverana Lauretti5, Carmelo Anile5, Cesare Colosimo3,6, Guido Rindi4,7, Alfredo Pontecorvi1, Laura De Marinis1, Antonio Bianchi1. 1. Dipartimento di Endocrinologia, Istituto di Patologia Speciale Medica, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy. 2. UOC di Radiologia e Diagnostica per Immagini, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Rome, Italy. 3. Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy. 4. Dipartimento di Anatomia Patologica, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy. 5. Dipartimento di Neurochirurgia, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy. 6. Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica e Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 7. Istituto di Patologia, Università Cattolica del Sacro Cuore, Rome, Italy.
Abstract
CONTEXT: The treatment of acromegaly resistant to first- and second-line therapies can be extremely challenging. DESIGN: We have described six patients who were successfully treated with a combination therapy of pasireotide and pegvisomant and compared them with a control group of patients resistant to conventional somatostatin analogs (SSAs), whose disease was controlled with other treatment, such as pasireotide (as monotherapy) or pegvisomant (as monotherapy or combined with conventional SSAs). RESULTS: In these six patients, acromegaly was controlled with combined pasireotide and pegvisomant treatment after failure of all other treatments. Compared with the 49 patients in the control group, these six patients had giant and invasive pituitary adenomas (at both the cavernous sinus and other structures). Although not statistically significant, higher growth hormone levels, more elevated Ki-67 expression, greater somatostatin receptor (SSTR) subtype 5 expression, and lower SSTR subtype 2 expression at the diagnosis of acromegaly were detected in patients receiving combination treatment with pasireotide and pegvisomant compared with the control group. CONCLUSION: Our data have reinforced the importance of personalized treatment of patients with acromegaly according to the clinical, biochemical, molecular, and morphological disease markers and suggest that combined treatment with pasireotide and pegvisomant can induce disease control in tumors with low SSTR2 expression, resistant to conventional SSAs (alone or combined with pegvisomant) and to new-generation SSAs alone (pasireotide).
CONTEXT: The treatment of acromegaly resistant to first- and second-line therapies can be extremely challenging. DESIGN: We have described six patients who were successfully treated with a combination therapy of pasireotide and pegvisomant and compared them with a control group of patients resistant to conventional somatostatin analogs (SSAs), whose disease was controlled with other treatment, such as pasireotide (as monotherapy) or pegvisomant (as monotherapy or combined with conventional SSAs). RESULTS: In these six patients, acromegaly was controlled with combined pasireotide and pegvisomant treatment after failure of all other treatments. Compared with the 49 patients in the control group, these six patients had giant and invasive pituitary adenomas (at both the cavernous sinus and other structures). Although not statistically significant, higher growth hormone levels, more elevated Ki-67 expression, greater somatostatin receptor (SSTR) subtype 5 expression, and lower SSTR subtype 2 expression at the diagnosis of acromegaly were detected in patients receiving combination treatment with pasireotide and pegvisomant compared with the control group. CONCLUSION: Our data have reinforced the importance of personalized treatment of patients with acromegaly according to the clinical, biochemical, molecular, and morphological disease markers and suggest that combined treatment with pasireotide and pegvisomant can induce disease control in tumors with low SSTR2 expression, resistant to conventional SSAs (alone or combined with pegvisomant) and to new-generation SSAs alone (pasireotide).
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