Tamoxifen Dose Escalation in Patients With Diminished CYP2D6 Activity Normalizes Endoxifen Concentrations Without Increasing Toxicity.

ABSTRACT:

Background

Polymorphic CYP2D6 is primarily responsible for metabolic activation of tamoxifen to endoxifen. We previously reported that by increasing the daily tamoxifen dose to 40 mg/day in CYP2D6 intermediate metabolizer (IM), but not poor metabolizer (PM), patients achieve endoxifen concentrations similar to those of extensive metabolizer patients on 20 mg/day. We expanded enrollment to assess the safety of CYP2D6 genotype-guided dose escalation and investigate concentration differences between races.

Methods

PM and IM breast cancer patients currently receiving tamoxifen at 20 mg/day were enrolled for genotype-guided escalation to 40 mg/day. Endoxifen was measured at baseline and after 4 months. Quality-of-life data were collected using the Functional Assessment of Cancer

SUBMITTER: Hertz DL 

PROVIDER: S-EPMC4943390 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature