bad23a7a0c9638ae3526eff340cd58dc 311675.pdf 46990097bc41edf4a392f98704b27e7a93d5bdf7 311675.pdf c250ac745fe990e68b5ea795ddc0e4d471ce11c6ea4d7a8dd27685229e7f1174 311675.pdf Title: Everolimus Through Plasmatic Concentrations in Cancer Patients: Prospective Longitudinal Observational Multicentric Study (DIANA-1 Project) Subject: Background: Everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR), is actually used to prevent organ transplant rejection and treat metastatic breast, renal, and neuroendocrine cancers. Despite significant pharmacokinetic variability among patients, routine therapeutic drug monitoring (TDM) is not commonly used in oncology. Methods: The aim of this multicenter, prospective observational cohort study is to assess the prevalence of everolimus minimum concentration at a steady state (Cminss) falling outside the therapeutic range (10–26.3 ng/mL) during a routine TDM programme. Sixty patients with metastatic breast, neuroendocrine, or renal cancers, either starting or continuing everolimus treatment according to hospital protocols, are to be included between 1st of January 2024 and 31st of December 2025 (patients undergoing clinical trials are excluded). We hypothesize that 30–50% of our patients and their blood samples will not achieve the target optimal plasma concentrations. Blood samples are collected every 4–6 weeks to monitor drug levels. The secondary goal is to explore correlation between out-of-range everolimus levels and factors such as demographic and anthropometric data, treatment specifics, lab results, genetic polymorphisms, and the presence of toxicity. Conclusions: This study could offer valuable insights into optimizing dosing strategies and may contribute to future research on personalizing everolimus and other anticancer treatments. This personalized approach seeks to tailor therapy not only to the tumour’s molecular profile but also to the individual characteristics of each patient, improving both drug selection and dosing precision. Keywords: everolimus; therapeutic drug monitoring; pharmacokinetic variability; optimal dosage; cancer Author: Eduard Fort-Casamartina, Sonia Pernas, Sara Otero, Paula Mate, Núria Gonzalo, Sonia Narváez, Raúl Rigo-Bonnin, Ariadna Padró-Miquel, Àlex Teulé, Xavier Garcia del Muro, Inma Peiró, Lorena Arribas, Anna Esteve, Andrea Gonzalez, Montse Rey, Ana Clopés, Sandra Fontanals and Carme Muñoz Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Mon Dec 30 05:13:41 2024 CET ModDate: Mon Dec 30 06:31:54 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 605851 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- TWQSRC+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 MDAWUY+URWPalladioL-Roma Type 1 Custom yes yes yes 16 0 ORXRMS+URWPalladioL-Bold Type 1 Custom yes yes yes 22 0 MNWTLX+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 QTOFRP+VnURWPalladioL Type 1 Custom yes yes yes 32 0 WSLXGC+CMSY10 Type 1 Builtin yes yes yes 58 0 JHYTSG+CMR10 Type 1 Builtin yes yes yes 72 0 OVNEXW+EURM10 Type 1 Builtin yes yes yes 80 0 ABKOIN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 98 0 ABKOIO+PalatinoLinotype CID TrueType Identity-H yes yes yes 101 0 ABKOIP+PalatinoLinotype TrueType WinAnsi yes yes no 107 0 ABKOJB+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 110 0 ABKPIM+PalatinoLinotype TrueType MacRoman yes yes no 113 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-07-09 02:41:27 CEST RepresentationInformation: 311675.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-07-08 19:20:01 CEST Size: 605851 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 276 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Background Destination: section.1 Item: Title: Material and Methods Destination: section.2 Children: Item: Title: Study Objective Destination: subsection.2.1 Item: Title: Hypothesis Destination: subsection.2.2 Item: Title: Study Design and Settings Destination: subsection.2.3 Item: Title: Ethics Destination: subsection.2.4 Item: Title: Inclusion Criteria Destination: subsection.2.5 Item: Title: Exclusion Criteria Destination: subsection.2.6 Item: Title: Study Procedures Destination: section.3 Children: Item: Title: Everolimus Treatment Destination: subsection.3.1 Item: Title: Adherence and Relative Dose Intensity Destination: subsection.3.2 Item: Title: Pharmacological Interaction Destination: subsection.3.3 Item: Title: Everolimus Therapeutic Drug Monitoring Destination: subsection.3.4 Item: Title: Genetic Variants Destination: subsection.3.5 Item: Title: Analytical Determination Destination: subsection.3.6 Item: Title: Body Composition and Anthropometry Destination: subsection.3.7 Item: Title: Samples Preparation and Storage Destination: subsection.3.8 Item: Title: Statistical Analysis Destination: subsection.3.9 Item: Title: Planned Study Period Destination: subsection.3.10 Item: Title: Data Management Destination: section.4 Item: Title: Discussion Destination: section.5 Item: Title: Conclusions Destination: section.6 Item: Title: References Destination: section.7 Info: Title: Everolimus Through Plasmatic Concentrations in Cancer Patients: Prospective Longitudinal Observational Multicentric Study (DIANA-1 Project) Author: Eduard Fort-Casamartina, Sonia Pernas, Sara Otero, Paula Mate, Núria Gonzalo, Sonia Narváez, Raúl Rigo-Bonnin, Ariadna Padró-Miquel, Àlex Teulé, Xavier Garcia del Muro, Inma Peiró, Lorena Arribas, Anna Esteve, Andrea Gonzalez, Montse Rey, Ana Clopés, Sandra Fontanals and Carme Muñoz Subject: Background: Everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR), is actually used to prevent organ transplant rejection and treat metastatic breast, renal, and neuroendocrine cancers. Despite significant pharmacokinetic variability among patients, routine therapeutic drug monitoring (TDM) is not commonly used in oncology. Methods: The aim of this multicenter, prospective observational cohort study is to assess the prevalence of everolimus minimum concentration at a steady state (Cminss) falling outside the therapeutic range (10 26.3 ng/mL) during a routine TDM programme. Sixty patients with metastatic breast, neuroendocrine, or renal cancers, either starting or continuing everolimus treatment according to hospital protocols, are to be included between 1st of January 2024 and 31st of December 2025 (patients undergoing clinical trials are excluded). We hypothesize that 30 50% of our patients and their blood samples will not achieve the target optimal plasma concentrations. Blood samples are collected every 4 6 weeks to monitor drug levels. The secondary goal is to explore correlation between out-of-range everolimus levels and factors such as demographic and anthropometric data, treatment specifics, lab results, genetic polymorphisms, and the presence of toxicity. Conclusions: This study could offer valuable insights into optimizing dosing strategies and may contribute to future research on personalizing everolimus and other anticancer treatments. This personalized approach seeks to tailor therapy not only to the tumour’s molecular profile but also to the individual characteristics of each patient, improving both drug selection and dosing precision. 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