title: EVESOR, a model-based, multiparameter, Phase I trial to optimize the benefit/toxicity ratio of everolimus and sorafenib.
abstract: OBJECTIVE
  This novel multiparameter Phase I study aimed to optimize doses/dosing schedules of everolimus and sorafenib drug combination, based on modeling/simulation (NCT01932177).
  
  
  METHODS
  About 26 patients with solid tumors were treated in four different dosing schedules. Everolimus once daily + sorafenib twice daily were given continuously in arms A and B, and intermittently in arms C (alternating every other week) and D (everolimus continuous and sorafenib 3 days on/4 days off).
  
  
  RESULTS
  Continuous schedules exhibited higher toxicity risks than intermittent schedules (64.1 vs 35.9%; p < 0.0001), and trends for lower disease control rates (80 vs 100%). No significant pharmacokinetic interaction was identified.
  
  
  CONCLUSIONS
  Feasibility of EVESOR trial is demonstrated. Intermittent schedules might provide better tolerance and efficacy than continuous schedules.
authors.affiliation: Faculté de Médecine Lyon-Sud, Univ Lyon, Université de Lyon, Université Claude Bernard Lyon 1, EMR UCBL/HCL 3738, Lyon, France.|National Research Centre, Pharmacology Department, Cairo, Egypt.
authors.forename: Mévidette
authors.initials: M
authors.lastname: El-Madani
authors.affiliation: Faculté de Médecine Lyon-Sud, Univ Lyon, Université de Lyon, Université Claude Bernard Lyon 1, EMR UCBL/HCL 3738, Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Colomban
authors.affiliation: Faculté de Médecine Lyon-Sud, Univ Lyon, Université de Lyon, Université Claude Bernard Lyon 1, EMR UCBL/HCL 3738, Lyon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Tod
authors.affiliation: Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Maillet
authors.affiliation: Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Peron
authors.affiliation: Faculté de Médecine Lyon-Sud, Univ Lyon, Université de Lyon, Université Claude Bernard Lyon 1, EMR UCBL/HCL 3738, Lyon, France.|Biochemistry & molecular biology department; Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Rodriguez-Lafrasse
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Osama A
authors.initials: OA
authors.lastname: Badary
authors.affiliation: Faculté de Médecine Lyon-Sud, Univ Lyon, Université de Lyon, Université Claude Bernard Lyon 1, EMR UCBL/HCL 3738, Lyon, France.|Radiology Department, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Valette
authors.affiliation: Faculté de Médecine Lyon-Sud, Univ Lyon, Université de Lyon, Université Claude Bernard Lyon 1, EMR UCBL/HCL 3738, Lyon, France.|Radiology Department, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Lefort
authors.affiliation: Phase 1 trial Unit, Centre Léon Bérard, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Cassier
authors.affiliation: National Research Centre, Pharmacology Department, Cairo, Egypt.
authors.forename: Siham M
authors.initials: SM
authors.lastname: El-Shenawy
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Ebtehal
authors.initials: E
authors.lastname: El-Demerdash
authors.affiliation: Faculté de Médecine Lyon-Sud, Univ Lyon, Université de Lyon, Université Claude Bernard Lyon 1, EMR UCBL/HCL 3738, Lyon, France.|Pathology Department, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Hommel-Fontaine
authors.affiliation: Faculté de Médecine Lyon-Sud, Univ Lyon, Université de Lyon, Université Claude Bernard Lyon 1, EMR UCBL/HCL 3738, Lyon, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Guitton
authors.affiliation: Biochemistry & molecular biology department; Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gagnieu
authors.affiliation: National Research Centre, Pharmacology Department, Cairo, Egypt.
authors.forename: Bassant Mm
authors.initials: BM
authors.lastname: Ibrahim
authors.affiliation: Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Barrois
authors.affiliation: Faculté de Médecine Lyon-Sud, Univ Lyon, Université de Lyon, Université Claude Bernard Lyon 1, EMR UCBL/HCL 3738, Lyon, France.|Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Freyer
authors.affiliation: Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: You
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D000068338:Everolimus / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D000077157:Sorafenib; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000068338:Everolimus; D000077157:Sorafenib
keywords: Phase I; administration and dosage; adverse events; angiogenesis inhibitors; everolimus; maximum tolerated dose; modeling; pharmacokinetics; solid tumor; sorafenib; targeted therapy