title: Individualised cancer chemotherapy: strategies and performance of prospective studies on therapeutic drug monitoring with dose adaptation: a review.
abstract: Therapeutic drug monitoring (TDM) is increasingly used in clinical practice for the optimisation of drug treatment. Although pharmacokinetic variability is an established factor involved in the variation of therapeutic outcome of many chemotherapeutic agents, the use of TDM in the field of oncology has been limited thus far. An important reason for this is that a therapeutic index for most anticancer agents has not been established; however, in the last 20 years, relationships between plasma drug concentrations and clinical outcome have been defined for various chemotherapeutic agents. Several attempts have been made to use these relationships for optimising the administration of chemotherapeutics by applying pharmacokinetically guided dosage. These prospective studies, individualising chemotherapy dose during therapy based on measured drug concentrations, are discussed in this review. We focus on the way a target value is defined, the methodologies used for dose adaptation and the way the performance of the dose-adaptation approach is evaluated. Furthermore, attention is paid to the results of the studies and the applicability of the strategies in clinical practice. It can be concluded that TDM may contribute to improving cancer chemotherapy in terms of patient outcome and survival and should therefore be further investigated.
authors.affiliation: Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands. apmil@slz.nl
authors.forename: Milly E
authors.initials: ME
authors.lastname: de Jonge
authors.forename: Alwin D R
authors.initials: AD
authors.lastname: Huitema
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Rodenhuis
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016903:Drug Monitoring / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents