| アブストラクト | Background: We described clinical features of adrenal insufficiency (AI) reported with tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Reports of AI recorded in FAERS (January 2004-March 2022) were identified through the high-level term "adrenal cortical hypofunctions". Demographic and clinical features were inspected, and disproportionality signals were detected through the Reporting Odds Ratio (ROR) and Information Component (IC) with relevant 95% confidence/credibility interval (CI), using different comparators and adjusting the ROR for co-reported corticosteroids and immune checkpoint inhibitors (ICIs). Results: Out of 147,153 reports with VEGFR-TKIs, 314 cases of AI were retained, mostly of which were serious (97.1%; hospitalization recorded in 44.9%). In a combination regimen with ICIs (43% of cases), VEGFR-TKIs were discontinued in 52.2% of the cases (26% as monotherapy). The median time to onset was 72 days (IQR = 14-201; calculated for 189 cases). A robust disproportionality signal emerged, also in comparison with other anticancer drugs (ROR = 2.71, 95%CI = 2.42-3.04; IC = 0.25, 95%CI = 0.07-0.39). Cabozantinib, sunitinib and axitinib generated robust disproportionality even after ROR adjustment. Conclusions: We call pharmacologists, internists, oncologists and endocrinologists to raise awareness of serious AI with VEGFR-TKIs, and to develop dedicated guidelines, especially for combination regimens with immunotherapy. |
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| ジャーナル名 | Cancers |
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| 投稿日 | 2022/10/15 |
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| 投稿者 | Raschi, Emanuel; Fusaroli, Michele; Giunchi, Valentina; Repaci, Andrea; Pelusi, Carla; Mollica, Veronica; Massari, Francesco; Ardizzoni, Andrea; Poluzzi, Elisabetta; Pagotto, Uberto; Di Dalmazi, Guido |
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| 組織名 | Pharmacology Unit, Department of Medical and Surgical Sciences (DIMEC), Alma;Mater Studiorum-University of Bologna, 40126 Bologna, Italy.;Division of Endocrinology and Diabetes Prevention and Care Unit, IRCCS Azienda;Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.;Department of Medical and Surgical Sciences (DIMEC), Alma Mater;Studiorum-University of Bologna, 40138 Bologna, Italy.;Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138;Bologna, Italy.;Department of Experimental, Diagnostic and Specialty Medicine, Policlinico S.;Orsola-Malpighi, Alma Mater Studiorum-University of Bologna, 40138 Bologna,;Italy. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/36230533/ |
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