Most patients on Tamoxifen receive a standard dose of medication. However, patients may benefit more from individually adjusted doses. This paper highlights potential strategies for personalized Tamoxifen treatments.
Tamoxifen is not active on its own. Once ingested, the body converts it into other substances (metabolites). Some of these metabolites, notably endoxifen, are responsible for most of the anti-cancer properties. Conversion of Tamoxifen into its active metabolites is done by enzymes called CYP2D6 and CYP3A. In some people these enzymes are damaged (mutated), lowering the body’s capacity to process Tamoxifen. Drugs such as some antidepressants may also interfere with the CYP2D6 and CYP3A enzymes.
Recent research suggest that the Tamoxifen regimen may be individualized according to enzyme capacity.
This article discusses the following strategies:
- CYP2D6 genotyping. Testing for mutated CYP2D6 can identify patients who may not be able to efficiently convert Tamoxifen into endoxifen. Unfortunately, mutations only accounted for about 39% of differences in endoxifen concentrations between individuals.
- CYP2D6 and CYP3A phenotyping. This strategy uses a ‘test drug’ (or “probe”) metabolized by the same enzymes as Tamoxifen to determine how well they work. This strategy was superior to genotyping in predicting endoxifen concentrations. However, this technique is still too complicated to introduce into common practice.
- Therapeutic drug monitoring (TDM). By regularly monitoring endoxifen concentrations in the blood, Tamoxifen doses may be adjusted (increasing the dose when endoxifen levels are low). However, current research has not yet identified the effective anti-cancer endoxifen level. Moreover, increasing the dose of Tamoxifen did not lead to higher endoxifen levels in all patients.
When adjusting the Tamoxifen regimen, any factor that interferes with its activity, like certain drugs (antidepressants) has to be taken into account. Personalized Tamoxifen treatment is possible, but further research is still needed to determine the best strategy.
Published By :
Clinical Pharmacology & Therapeutics
Oct 01, 2012
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