title: Multiparameter Phase I trials: a tool for model-based development of targeted agent combinations--example of EVESOR trial.
abstract: Optimal development of targeted drug combinations is one of the future challenges to be addressed. Computerization and mathematical models able to describe biological phenomena and to simulate the effects of changes in experimental conditions may help find solutions to this issue. We propose the concept of 'multiparameter trials', where biological, radiological and clinical data required for modeling purpose are collected and illustrated by the ongoing academic EVESOR trial. The objective of the model-based work would be the determination of the optimized doses and dosing schedules of everolimus and sorafenib, offering the maximization of the predicted modeled benefit/toxicity ratio in patients with solid tumors. It may embody the 'proof of concept' of model-based drug development of anticancer agent combinations.
authors.affiliation: EMR UBCL/HCL 3738, Université Claude Bernard Lyon-1, Lyon, France.
authors.forename: Mevidette
authors.initials: M
authors.lastname: El-Madani
authors.forename: Emilie
authors.initials: E
authors.lastname: Hénin
authors.forename: Thibaud
authors.initials: T
authors.lastname: Lefort
authors.forename: Michel
authors.initials: M
authors.lastname: Tod
authors.forename: Gilles
authors.initials: G
authors.lastname: Freyer
authors.forename: Philippe
authors.initials: P
authors.lastname: Cassier
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Valette
authors.forename: Claire
authors.initials: C
authors.lastname: Rodriguez-Lafrasse
authors.forename: Francoise
authors.initials: F
authors.lastname: Berger
authors.forename: Jérome
authors.initials: J
authors.lastname: Guitton
authors.forename: Joel
authors.initials: J
authors.lastname: Lachuer
authors.forename: Khemaies
authors.initials: K
authors.lastname: Slimane
authors.forename: Catherine
authors.initials: C
authors.lastname: Barrois
authors.forename: Benoit
authors.initials: B
authors.lastname: You
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D000068338:Everolimus / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D008962:Models, Theoretical; D058990:Molecular Targeted Therapy; 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 / Q000493:pharmacokinetics; D000077157:Sorafenib; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000068338:Everolimus; D000077157:Sorafenib
keywords: Phase I; angiogenesis inhibitors; clinical trial; drug therapy; everolimus; modeling; pharmacokinetics; solid tumor; sorafenib; targeted therapy; toxicity