BACKGROUND CYP3A5 genotyping might be useful to guide tacrolimus and sirolimus dosing. The aim of this study was to assess the influence of CYP3A5 polymorphism on everolimus metabolism and pharmacokinetics. METHODS We investigated the effect of CYP3A5 6986A>G polymorphism (CYP3A5*1/*3 alleles) on the pharmacokinetics of everolimus in 28 renal transplant patients and on its in vitro hepatic me...

The incidence of neuroendocrine tumors (NET) has increased dramatically in the past 30 years. This information has revitalized basic and clinical research into the molecular biology of NET and has resulted in the recent approval of new therapies for pancreatic NET (pNET), including the oral inhibitor of the mTOR everolimus. Everolimus significantly improved progression-free survival among patie...

Despite advances in immunosuppressive therapy, long-term renal-transplantation outcomes have not significantly improved over the last decade. The nephrotoxicity of calcineurin inhibitors (CNIs) is an important cause of chronic allograft nephropathy (CAN), the major driver of long-term graft loss. Everolimus is a proliferation signal inhibitor with a mechanism of action that is distinct from CNI...

OBJECTIVE To assess the efficacy and safety of everolimus in Japanese patients with metastatic renal cell carcinoma. METHODS A subgroup analysis of the pivotal Phase III, randomized, double-blind, placebo-controlled trial of everolimus 10 mg/day in patients with disease progression after treatment with sorafenib, sunitinib or both assessed outcomes in Japanese participants. Results were compa...

Activation of the mammalian target of rapamycin (mTOR) signaling pathway is an important mechanism of resistance to endocrine therapy in breast cancer. Everolimus, an mTOR inhibitor, has been shown to increase the efficacy of endocrine therapy and overcome resistance to endocrine therapies. Clinical studies have suggested that everolimus combined with endocrine therapy prolongs progression-free...

OBJECTIVE Lymphangioleiomyomatosis (LAM) is a rare systemic disease of young women arising from mutations in the tuberous sclerosis complex (TSC) genes, TSC1 or TSC2. This disrupts the mammalian target of rapamycin (mTOR) pathway, affecting cellular proliferation and growth. mTOR inhibitors are a promising novel therapy in LAM. The mTOR inhibitor sirolimus is reported to produce resolution of l...

Cardiac rhabdomyoma often shows spontaneous regression and usually requires only close follow-up. However, patients with symptomatic inoperable rhabdomyomas may be candidates for everolimus treatment. Our patient had multiple inoperable cardiac rhabdomyomas causing serious left ventricle outflow-tract obstruction that showed a dramatic reduction in the size after everolimus therapy, a mammalian...

BACKGROUND Everolimus was recently approved for the treatment of neuroendocrine tumors. However, its efficacy and tolerability in hemodialysis patients with end-stage renal disease is not established. CASE PRESENTATION We describe the case of a 47-year-old man with end-stage renal disease who received everolimus plus Lanreotide for 9 months for the management of metastatic atypical bronchial ...

While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3/*3. The purpose of this study was to evaluate how the area under the blood concentration-time curves (AUC) of tacrolimus could be predicted based on CYP3A5 genotype and the AUC of everolimus in renal transplant patients taking both drugs. Th...

The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into account, all de novo heart transplant patients can be regarded as potential candidates for immunosuppression with everolimus and reduced-expos...