Without therapeutic drug monitoring, there is no personalized cancer care.

TDM and exposure–response relationships TDM is the measurement and interpretation of drug concentrations in biological fluids so as to determine the correct drug dosage for an individual patient.1 The technique requires that dose be correlated with exposure and that exposure be correlated with pharmacodynamic (PD) response. Exposure metrics include the pharmacokinetic (PK) parameters: area under the plasma concentration–time curve, time above threshold concentration, maximum concentration, and trough. Area under the plasma concentration–time curve is often used, but trough will probably be a more widely assessed metric in the future thanks to its practicality with respect to daily-dosed, long-half-life tyrosine kinase inhibitors (TKIs). PD responses that can be correlated with exposure are efficacy and toxicity. A single dose may result in a range of exposures (PK variability), and a single exposure may result in a range of responses (PD variability) (Figure 1). Previously established exposure–response relationships can be the basis for determining the therapeutic target window. By creating a distribution of doses, TDM can correct for most of the PK variability, consequently reducing the variability in responses. A current guidance from the US Food and Drug Administration describes exploration of the relationship between exposure and response at a population level that may include mere dose– response relationships. For TDM, first a PD response is shown to correlate with exposure in individuals, often retrospectively. Next, a prospective study should validate the effect of TDM intervention on patient outcome.