title: Nonlinear model predictive control for dosing daily anticancer agents using a novel saturating-rate cell-cycle model.
abstract: A nonlinear model predictive control (NMPC) algorithm was developed to dose the chemotherapeutic agent tamoxifen based on a novel saturating-rate, cell-cycle model (SCM). Using daily tumor measurements, the algorithm decreased tumor volume along a specified reference trajectory in simulated animals over 4 months. In mismatch case studies, controllers based on the Gompertz model (GM) yielded equivalent total drug delivered and elapsed time to t(99%) reference step convergence to those obtained using the SCM, though this performance was dependent on the cell-cycle phase of drug effect. Overall, the NMPC algorithm is suitable for dosing chemotherapeutics with regular administration schedules and may be adapted for regularly administered chemotherapeutics other than tamoxifen.
authors.affiliation: Department of Chemical and Petroleum Engineering, University of Pittsburgh School of Engineering, Pittsburgh, PA, USA.
authors.forename: Jeffry A
authors.initials: JA
authors.lastname: Florian
authors.forename: Julie L
authors.initials: JL
authors.lastname: Eiseman
authors.forename: Robert S
authors.initials: RS
authors.lastname: Parker
mesh_terms: D000465:Algorithms; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017711:Nonlinear Dynamics; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D013629:Tamoxifen