Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles

Trial Information

Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles

Aromatase inhibitors (AIs) are widely used as adjuvant treatment for estrogen-receptor
positive breast cancer in post-menopausal women. AIs have been demonstrated to have equal to
or greater efficacy and less toxicity than tamoxifen (TAM), the drug of choice for many
years. Exemestane (EXE) is a 3rd-generation AI that has demonstrated efficacy in the
treatment of breast cancer patients, and as with TAM and other AIs, there has been
considerable inter-individual variability in overall response to EXE and in the occurrence
of toxicities, but the causes of this variability have not been elucidated. Differences in
drug metabolism can be a source of variability between patients. Genetic variations occur in
several of the enzymes involved in phase I and II metabolic reactions and many of these can
lead to alterations in enzyme activity which in turn can alter therapeutic response to
drugs. EXE is extensively metabolized as unchanged EXE and is found at less than 1% in urine
and 10% in plasma. EXE pharmacokinetics will be established in a series of 20 subjects
taking EXE. EXE metabolites will then be measured at an optimal time post-EXE dose in the
urine of 200 breast cancer patients being treated with EXE to establish whether metabolizing
enzyme genotype-EXE metabolism phenotype correlations exist in vivo.