Biomedical Engineering Reference
In-Depth Information
cross-validation is a general problem that should be prioritized amongst the clinical
pharmacology community working in the field of targeted anticancer therapy.
Initially, external quality control program have been organized for imatinib at the
Bordeaux University Hospital (France) within the frame European Treatment and
Outcome Study (EUTOS) of the European Leukemia Net [
267
] . Some private labo-
ratories currently provide external quality control samples for imatinib, nilotinib
and dasatinib [
268
]. Given the growing armamentarium anticipated for targeted
anticancer therapy in the next decade, a reinforced analytical collaboration must be
deployed between laboratories for harmonizing the assays for current and new TKIs
to come, as well as for tamoxifen and metabolites, and possibly also for other anti-
cancer endocrine agents administered chronically (i.e., aromatase inhibitors) as well
as the m-TOR inhibitor everolimus, increasingly used in oncology. Beyond working
out analytical issues, collaborative research efforts should also be devoted to struc-
turing the collection of data internationally, so that translational research aimed at
understanding pharmacokinetics, pharmacodynamics, pharmacogenetics of newest
anticancer-targeted therapy will allow without delay the return to clinicians of rel-
evant measurements and their validated interpretations. The systematic and efficient
collection of accurate clinical information along with TDM samples indeed repre-
sents no less challenging issues that the measurement of those samples.
In complement to the diagnostic tests already approved for selecting patients
who are more likely to benefit from a given anticancer treatment [
5
] , individualiza-
tion of TKIs drug dosage by TDM represents the next step towards a further
refinement for targeted anticancer therapies, aiming at administering “the right dose
of the right drug to the right patient.” In this emerging field of personalized medi-
cine, the development of TDM for patient-tailored dose adjustment should allow to
maximize both the therapeutic benefit and the tolerability of these new drugs. These
issues are certainly relevant both to individual patients, given the frequency of
suboptimal clinical responses, toxicities, intolerance, and treatment discontinua-
tions, and to the society, given the elevated costs of TKIs treatments and of their
shortcomings.
Acknowledgments
This chapter has been realized within the frame of the research project
“Integrative cellular pharmacokinetics/pharmacodynamics/pharmacoproteomics studies of anti-
cancer TKIs in leukemia” (SNF grant no. 310030_138097/1 to LAD) supported by the Swiss
National Science Foundation (SNF, Switzerland). It also benefited from the support of the SNF-
funded initiative Nano-Tera (ISyPeM project [
269
] to TB).
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