Most of the novel targeted anticancer agents share classical
characteristics that define drugs as candidates for blood concentration
monitoring: long-term therapy; high interindividual but
restricted intraindividual variability; significant drug-drug and drug-
food interactions; correlations between concentration and efficacy/
toxicity with rather narrow therapeutic index; reversibility of effects;
and absence of early markers of response. Surprisingly though, therapeutic
concentration monitoring has received little attention for these
drugs despite reiterated suggestions from clinical pharmacologists.
Several issues explain the lack of clinical research and development
in this field: global tradition of empiricism regarding treatment
monitoring, lack of formal conceptual framework, ethical difficulties
in the elaboration of controlled clinical trials, disregard from
both drug manufacturers and public funders, limited encouragement
from regulatory authorities, and practical hurdles making dosage
adjustment based on concentration monitoring a difficult task for
prescribers. However, new technologies are soon to help us overcome
these obstacles, with the advent of miniaturized measurement devices
able to quantify circulating drug concentrations at the point-of-care,
to evaluate their plausibility given actual dosage and sampling time,
to determine their appropriateness with reference to therapeutic targets,
and to advise on suitable dosage adjustment. Such evolutions
could bring conceptual changes into the clinical development of drugs
such as anticancer agents, while increasing the therapeutic impact of
population PK-PD studies and systematic reviews. Research efforts
in that direction from the clinical pharmacology community will
be essential for patients to receive the greatest benefits and the least
harm from new anticancer treatments. The example of imatinib, the
first commercialized tyrosine kinase inhibitor, will be outlined to
illustrate a potential research agenda for the rational development
of therapeutic concentration monitoring.