title: A tool for neutrophil guided dose adaptation in chemotherapy.
abstract: Chemotherapy dosing in anticancer treatment is a balancing act between achieving concentrations that are effective towards the malignancy and that result in acceptable side-effects. Neutropenia is one major side-effect of many antitumor agents, and is related to an increased risk of infection. A model capable of describing the time-course of myelosuppression from administered drug could be used in individual dose selection. In this paper we describe the transfer of a previously developed semi-mechanistic model for myelosuppression from NONMEM to a dosing tool in MS Excel, with etoposide as an example. The tool proved capable to solve a differential equation system describing the pharmacokinetics and pharmacodynamics, with estimation performance comparable to NONMEM. In the dosing tool the user provides neutrophil measures from a previous treatment course and request for the dose that results in a desired nadir in the upcoming course through a Bayesian estimation procedure.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. johan.wallin@farmbio.uu.se
authors.forename: Johan E
authors.initials: JE
authors.lastname: Wallin
authors.forename: Lena E
authors.initials: LE
authors.lastname: Friberg
authors.forename: Mats O
authors.initials: MO
authors.lastname: Karlsson
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D024221:Antineoplastic Protocols; D001499:Bayes Theorem; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000503:physiopathology; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D009503:Neutropenia / Q000139:chemically induced / Q000503:physiopathology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide