A tool for neutrophil guided dose adaptation in chemotherapy

Comput Methods Programs Biomed. 2009 Mar;93(3):283-91. doi: 10.1016/j.cmpb.2008.10.011. Epub 2008 Dec 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Antineoplastic Protocols*
  • Bayes Theorem
  • Bone Marrow Diseases / chemically induced
  • Bone Marrow Diseases / physiopathology
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Etoposide / pharmacokinetics
  • Etoposide / therapeutic use
  • Humans
  • Neutropenia / chemically induced
  • Neutropenia / physiopathology
  • Neutrophils / cytology*
  • Neutrophils / drug effects*

Substances

  • Antineoplastic Agents, Phytogenic
  • Etoposide