Background. Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs. PatientsandMethods. Asystematicreviewof thepublisheddata was performed concerning the use of everolimus in extrapancreaticNET, with theaimofsummarizing thecurrent knowledgeonits efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary. Results. The present study included 22 different publications, including 874 patients and 456 extrapancreatic NETs treated with everolimus. Nine different primary sites of extrapancreatic NETs were found. The median progression-free survival ranged from 12.0 to 29.9months.Themedian time to progression was not reached in a phase II prospective study, and the interval to progression ranged from 12 to 36 months in 5 clinical cases. Objective responses were observed in 7 prospective studies, 2 retrospective studies, and 2 case reports. Stabilization of the disease was obtained in a high rate of patients, ranging from 67.4% to 100%. The toxicity of everolimus in extrapancreatic NETs is consistent with the known safety profile of the drug. Most adverse events were either grade 1 or 2 and easy manageable with a dose reduction or temporary interruption and only rarely requiring discontinuation. Conclusion. Treatment with everolimus in patients with extrapancreatic NETs appears to be a promising strategy that is safe and well tolerated.The use of this emerging opportunity needs to be validated with clinical trials specifically designed on this topic.

Faggiano A., Malandrino P., Modica R., Agrimi D., Aversano M., Bassi V., et al. (2016). Efficacy and safety of everolimus in extrapancreatic neuroendocrine tumor: A comprehensive review of literature. THE ONCOLOGIST, 21(7), 875-886 [10.1634/theoncologist.2015-0420].

Efficacy and safety of everolimus in extrapancreatic neuroendocrine tumor: A comprehensive review of literature

Malandrino P.;Modica R.;Bassi V.;Guarnotta V.;Nicastro V.;Nuzzo V.;
2016-01-01

Abstract

Background. Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs. PatientsandMethods. Asystematicreviewof thepublisheddata was performed concerning the use of everolimus in extrapancreaticNET, with theaimofsummarizing thecurrent knowledgeonits efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary. Results. The present study included 22 different publications, including 874 patients and 456 extrapancreatic NETs treated with everolimus. Nine different primary sites of extrapancreatic NETs were found. The median progression-free survival ranged from 12.0 to 29.9months.Themedian time to progression was not reached in a phase II prospective study, and the interval to progression ranged from 12 to 36 months in 5 clinical cases. Objective responses were observed in 7 prospective studies, 2 retrospective studies, and 2 case reports. Stabilization of the disease was obtained in a high rate of patients, ranging from 67.4% to 100%. The toxicity of everolimus in extrapancreatic NETs is consistent with the known safety profile of the drug. Most adverse events were either grade 1 or 2 and easy manageable with a dose reduction or temporary interruption and only rarely requiring discontinuation. Conclusion. Treatment with everolimus in patients with extrapancreatic NETs appears to be a promising strategy that is safe and well tolerated.The use of this emerging opportunity needs to be validated with clinical trials specifically designed on this topic.
Settore MED/13 - Endocrinologia
http://theoncologist.alphamedpress.org/content/21/7/875.full.pdf
Faggiano A., Malandrino P., Modica R., Agrimi D., Aversano M., Bassi V., et al. (2016). Efficacy and safety of everolimus in extrapancreatic neuroendocrine tumor: A comprehensive review of literature. THE ONCOLOGIST, 21(7), 875-886 [10.1634/theoncologist.2015-0420].
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