title: Optimal response to chemotherapy for a mathematical model of tumor-immune dynamics.
abstract: An optimal control problem for cancer chemotherapy is considered that includes immunological activity. In the objective a weighted average of several quantities that describe the effectiveness of treatment is minimized. These terms include (i) the number of cancer cells at the terminal time, (ii) a measure for the immunocompetent cell densities at the terminal point (included as a negative term), (iii) the overall amount of cytotoxic agents given as a measure for the side effects of treatment and (iv) a small penalty on the terminal time that limits the overall therapy horizon which is assumed to be free. This last term is essential in obtaining a well-posed problem formulation. Employing a Gompertzian growth model for the cancer cells, for various scenarios optimal controls and corresponding responses of the system are calculated. Solutions initially follow a full dose treatment, but then at one point switch to a singular regimen that only applies partial dosages. This structure is consistent with protocols that apply an initial burst to reduce the tumor volume and then maintain a small volume through lower dosages. Optimal controls end with either a prolonged period of no dose treatment or, in a small number of scenarios, this no dose interval is still followed by one more short burst of full dose treatment.
authors.affiliation: Department of Mathematics and Statistics, Southern Illinois University at Edwardsville, Edwardsville, IL 62026-1653, USA. uledzew@siue.edu
authors.forename: Urszula
authors.initials: U
authors.lastname: Ledzewicz
authors.forename: Mohammad
authors.initials: M
authors.lastname: Naghnaeian
authors.forename: Heinz
authors.initials: H
authors.lastname: Schättler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents