Individualized Tamoxifen Dose Escalation: Confirmation of Feasibility, Question of Utility

Abstract

Tamoxifen may require metabolic activation to endoxifen for efficacy in treating hormone receptor-positive breast cancer. Dose escalation in patients with low endoxifen concentrations could enhance treatment efficacy. This approach is clinically feasible, and successfully increases endoxifen concentrations; however, it is unknown whether patients benefit from individualized tamoxifen dose escalation. Clin Cancer Res; 22(13); 3121-3. ©2016 AACRSee related article by Fox et al., p. 3164.

Figure 1. Illustration of 9 patients matriculating through an integrated personalized treatment strategy

Baseline information including CYP2D6 phenotype (poor (PM), intermediate (IM), or extensive (EM) metabolizer) and clinical information (body mass index, drug-drug interactions, etc.) are used to predict endoxifen concentration during treatment with the typical dose of 20 mg/day. Patients predicted to be above the efficacy threshold (hatched green horizontal line) are started at the typical dose. Patients predicted to be below the threshold are pre-emptively dose escalated by 10 or 20 mg/day. After 1 month of treatment, endoxifen concentration is measured to determine whether further dose personalization is necessary. Some patients who were not expected to require escalation (i.e. #2) have sub-therapeutic concentration and require a dose increase. Other patients who had a dose escalation (i.e. #8) require further escalation to reach therapeutic endoxifen levels. Ultimately, all patients achieve therapeutic endoxifen concentrations, maximizing tamoxifen treatment effectiveness.