Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors

Interpatient (and intrapatient) variability in pharmacokinetics may be a major
determinant in targeted anticancer therapy outcome since this may lead to
unpredictable efficacy and safety. In case of imatinib, there is already
emerging evidence for a relationship between plasma levels and clinical
efficacy/occurrence of side effects. Knowledge of this PK-PD relationship can
be used to optimize therapy in order to prevent failure of targeted anti-cancer
agents by monitoring of drug resistance and reducing drug toxicity. Since the
burden of therapy is severe and targeted anti-cancer therapy is very expensive
(> ¤ 2000 / month) monitoring of plasma drug levels in order to optimise
therapy is likely to be cost effective. Since all targeted anti-cancer agents
have large similarities in mechanism of action and target proteins within their
drug class, similar PK-PD relations are to be expected for all targeted
anti-cancer agents within these drug classes. This underlines the rationale for
a structured prospective follow up of patients using any targeted anti-cancer
agent.

Primary:
To determine the pharmacokinetics of several clinically used targeted
anti-cancer agents.

Secondary:
To examine the relationship between treatment response/toxicity and plasma (or
intracellular) drug levels.
To evaluate the specific influence of different parameters on variability in
pharmacokinetics and -dynamics

A longitudinal follow up cohort study of all patients using a targeted
anti-cancer agent for treatment of cancer.

The sampling scheme of the NIB-cohort study will be minimally invasive. In the
NIB-cohort all sampling is carried out during routine follow up for targeted
anti-cancer therapy and does not require additional vena punctures. The benefit
for the participating patients exists of individual treatment optimisation by
routinely applied TDM using the knowledge concerning PK-PD relations of
targeted anti-cancer agents acquired from the NIB-cohort study.