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 infecti...

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Bibliographic Details
Published in:Computer methods and programs in biomedicine 2009-03, Vol.93 (3), p.283-291
Main Authors: Wallin, Johan E, Friberg, Lena E, Karlsson, Mats O
Format: Article
Language:English
Subjects:
Adaptive control
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Agents, Phytogenic - pharmacokinetics
Antineoplastic Agents, Phytogenic - therapeutic use
Antineoplastic Protocols
Bayes Theorem
Bayesian forecasting
Biofarmaci
biomarker
Biopharmacy
Bone Marrow Diseases - chemically induced
Bone Marrow Diseases - physiopathology
Dose adaptation
Drug Administration Schedule
Etoposide - administration & dosage
Etoposide - pharmacokinetics
Etoposide - therapeutic use
Farmaceutisk farmakologi
FARMACI
Farmakokinetik och läkemedelsterapi
Humans
Internal Medicine
Myelosuppression
Neutropenia
Neutropenia - chemically induced
Neutropenia - physiopathology
Neutrophils - cytology
Neutrophils - drug effects
Other
Pharmaceutical pharmacology
Pharmacodynamics
Pharmacokinetics and Drug Therapy
PHARMACY
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Summary: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.
ISSN:0169-2607
1872-7565
1872-7565
DOI:10.1016/j.cmpb.2008.10.011