Metabolizing Enzyme Genotype Versus Exemestane Metabolism Profiles
| Status: | Completed |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/27/2018 |
| Start Date: | September 2011 |
| End Date: | May 1, 2018 |
It is the investigators hypothesis that exemestane (EXE) metabolism is an important source of
the inter-individual variation in EXE metabolic profiles and that polymorphisms in
EXE-metabolizing enzymes may potentially play a role in affecting EXE therapeutic efficacy
and toxicity. The goals of this clinical study are to (1) establish EXE metabolism profile
kinetics, and (2) determine whether correlations exist in vivo between metabolizing enzyme
genotype and urinary EXE metabolite profiles in women being treated with EXE. Together, these
studies will allow us to fully characterize functionally-relevant polymorphisms in the
EXE-metabolizing enzyme pathway that are potentially important in EXE clinical efficacy.
the inter-individual variation in EXE metabolic profiles and that polymorphisms in
EXE-metabolizing enzymes may potentially play a role in affecting EXE therapeutic efficacy
and toxicity. The goals of this clinical study are to (1) establish EXE metabolism profile
kinetics, and (2) determine whether correlations exist in vivo between metabolizing enzyme
genotype and urinary EXE metabolite profiles in women being treated with EXE. Together, these
studies will allow us to fully characterize functionally-relevant polymorphisms in the
EXE-metabolizing enzyme pathway that are potentially important in EXE clinical efficacy.
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.
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.
Inclusion Criteria:
- Breast cancer patients who have ER+ tumors and are taking 25 mg EXE daily (orally)
- Post-menopausal women or chemically post-menopausal women (who won't become pregnant
since they are taking zoladex), or women who are post-menopausal as a result of ovary
removal
- Patients may be at any point in their hormonal treatment, but must have completed any
planned surgery, radiation and chemotherapy.
Exclusion Criteria:
- Concurrent use of corticosteroids, megestrol, or phenobarbitol (inhaled and internasal
steroids are permitted)
- History of allergy to exemestane
We found this trial at
1
site
500 University Dr
Hershey, Pennsylvania 17033
Hershey, Pennsylvania 17033
(717) 531-6955
Penn State Milton S. Hershey Medical Center Penn State Milton S. Hershey Medical Center, Penn...
Click here to add this to my saved trials
