title: Practical management of everolimus-related toxicities in patients with advanced solid tumors.
abstract: Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), an intracellular protein kinase downstream of the phosphatidylinositol 3-kinase/AKT pathway involved in key components of tumorigenesis, including cell growth, proliferation, and angiogenesis. In the advanced cancer setting, based on favorable results from phase III trials, everolimus is indicated for the treatment of advanced renal cell carcinoma, advanced neuroendocrine tumors of pancreatic origin, and advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Additional oncology indications for everolimus include renal angiomyolipoma with tuberous sclerosis complex and subependymal giant-cell astrocytoma. Although it is generally well tolerated, with most adverse events of mild to moderate severity and manageable, everolimus exhibits a distinct adverse event profile that warrants guidance for proper diagnostic and medical management. This guidance is particularly important given the potential for widespread long-term use of everolimus. This review will focus on the most relevant toxicities associated with mTOR inhibitors and on their management. Practical treatment recommendations are presented for stomatitis, noninfectious pneumonitis, rash, selected metabolic abnormalities, and infections. Provided these events are rapidly identified and treated, the vast majority should resolve with minimal effect on treatment outcomes and patients' quality of life.
authors.affiliation: Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Germany. gruenwald.viktor@mh-hannover.de
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Pavel
authors.forename: Dieter
authors.initials: D
authors.lastname: Hörsch
authors.forename: Diana
authors.initials: D
authors.lastname: Lüftner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.forename: Matthias
authors.initials: M
authors.lastname: Geberth
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Weber
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000068338:Everolimus; D006801:Humans; D017053:Infection Control / Q000379:methods*; D007239:Infections / Q000139:chemically induced*; D007249:Inflammation / Q000139:chemically induced* / Q000517:prevention & control*; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; D020123:Sirolimus