Therapeutic drug monitoring of cancer chemotherapy

Abstract

Therapeutic drug monitoring is not routinely used for chemotherapy agents. There are Several reasons, but one major drawback is the lack of established therapeutic Concentration ranges. Combination chemotherapy makes the establishment of Therapeutic ranges for individual drugs difficult, the concentration-effect relationship for a single drug may not be the same as when that drug is used in a drug combination. Pharmacokinetic optimization protocols for many classes of cytotoxic compounds exist in specialized centers, and some of these protocols are now part of large multicentre trials. Nonetheless, TDM clearly has the potential to improve the clinical use of chemotherapy gents, most of which have very narrow therapeutic indices and highly variable pharmacokinetics. A substantial body of literature accumulating during the past 15 years demonstrates relationships between systemic exposure to various chemotherapy agents and their toxic or therapeutic effects. This article reviews TDM concepts in addition to tools based on pharmacokinetic modeling of chemotherapy agents. The administered dose of chemotherapy agents is sometimes adjusted individually using either a priori or a posteriori methods. These models can only be applied by using the same dose and schedule as the original study. Bayesian estimation offers more flexibility in blood sampling times and, owing to its precision and to the amount of information provided is the method of choice for ensuring that a given patient benefits from the desired systemic exposure. Moreover, the role and application of Pharmacogenetics as a tool for individualizing chemotherapy is discussed highlighting the agents and mechanisms that have been well studied and defined and their relevance to clinical practice. Finally, this paper address issues critical to the optimal use of TDM in a clinical setting, and the role of clinical pharmacist in this regard. In addition, it discusses future developments in this field that can contribute to improving cancer chemotherapy In terms of patient outcome and survival.

A new HPLC UV validated method for therapeutic monitoring of deferasirox in thalassaemic patients

“…Measurement of DFX plasma concentrations in treated patients, in fact, could be useful to evaluate patient adherence to daily oral therapy, potential drug-drug interactions, and pharmacokinetic (PK)/pharmacodynamic (PD) relationship studies [16] and [17]. Furthermore recent data [18] show an inverse correlation between preadministration labile plasma iron, target of chelators, and DFX trough concentration (i.e.…”

Therapeutic Drug Monitoring in Cancer Chemotherapy

“…The Bayesian method assumes that each patient is a member of a specific population defined by the values intrinsic to the population. This allows for the possibility of having only one blood sampling per patient, compared with multiple sampling ith other methods, and thus provides the flexibility to accommodate the few data points at suboptimal time points that may be seen in some clinical settings [37].…”

“…A priori method A priori methods allow the estimation of the dose necessary to reach a target exposure in a given patient using morphological, biological and physiological data such as body weight, age, gender, serum creatinine level and GFR [37]. The dosing of carboplatin by Calvert's and Chatelut's formulas provides an important example of how individual dose estimation is determined using the a priori method.…”

“…Conversely, Chatelut's formula was developed using pharmacokinetic modeling that requires age, gender, weight and serum creatinine levels [39]. Although a priori methods account for some interindividual pharmacokinetic variability, their performance is not as good as that of a posteriori methods because there is a typical variability of 20% [37].…”

Pharmacogenetic Tests in Ukraine: Economic Aspect

“…The relevance of pharmacogenetic testing is stipulated by occurrence of side effects of treatment when underestimating the genetic polymorphism of the systems involved in the metabolism of drugs. Side effects related to genetic differences between people are especially evident in the treatment of cancer (3).…”