Nonlinear model predictive control for dosing daily anticancer agents using a novel saturating-rate cell-cycle model.
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.
Florian
Jeffry A
JA
Department of Chemical and Petroleum Engineering, University of Pittsburgh School of Engineering, Pittsburgh, PA, USA.
Eiseman
Julie L
JL
Parker
Robert S
RS
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
D000970:Antineoplastic Agents; D013629:Tamoxifen