Relationship between everolimus exposure and safety and efficacy: Meta-analysis of clinical trials in oncology

• Published in: European journal of cancer (1990) Vol. 50; no. 3; pp. 486 - 495
• Main Authors: Ravaud, Alain, Urva, Shweta R., Grosch, Kai, Cheung, Wing K., Anak, Oezlem, Sellami, Dalila B.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.02.2014; Elsevier
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; ATP Binding Cassette Transporter, Subfamily B, Member 1 - antagonists & inhibitors; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Biological and medical sciences; Cancer; Clinical Trials as Topic; Cytochrome P-450 CYP3A - metabolism; Cytochrome P-450 CYP3A Inhibitors; Disease-Free Survival; Efficacy; Everolimus; Hematology, Oncology and Palliative Medicine; Humans; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - drug therapy; Neoplasms - metabolism; Pharmacokinetics; Pharmacology. Drug treatments; Randomized Controlled Trials as Topic; Safety; Sirolimus - administration & dosage; Sirolimus - adverse effects; Sirolimus - analogs & derivatives; Sirolimus - pharmacokinetics; Tumors; Efficacy; Safety; Pharmacokinetics; Everolimus; Cancer; Toxicity; Treatment efficiency; Lactone; Exposure; Malignant tumor; Macrolide; Metaanalysis; Cancerology; Clinical trial; Protein synthesis inhibitor; Immunosuppressive agent

In patients with solid tumours, daily everolimus dosing demonstrated dose proportionality and linear pharmacokinetics. A meta-analysis was conducted to characterise the relationship between everolimus Cmin and efficacy and safety and the effect of CYP3A4 and P-glycoprotein (PgP) substrate/inhibitor/...