Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226 Journal Article


Authors: Hertz, D. L.; Barlow, W. E.; Kidwell, K. M.; Albain, K. S.; Vandenberg, T. A.; Dakhil, S. R.; Tirumali, N. R.; Livingston, R. B.; Gralow, J.; Hayes, D. F.; Hortobagyi, G. N.; Mehta, R. S.; Rae, J. M.
Article Title: Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226
Abstract: AIMS: In the SWOG S0226 trial the combination of anastrozole plus fulvestrant (n=349) was superior to anastrozole alone (n=345) in hormone receptor (HR)-positive metastatic breast cancer. Here we report a pharmacokinetic subset analysis investigating a possible drug interaction between anastrozole and fulvestrant. METHODS: Post-menopausal patients with HR-positive metastatic breast cancer were randomized to anastrozole with or without concurrent fulvestrant. Blood samples were collected at 2, 4, 6, and 8 months, just prior to receiving the next dose of anastrozole and fulvestrant. Drug concentrations were measured via LC/MS-MS. Anastrozole concentration was compared in patients on anastrozole alone vs. patients on concomitant fulvestrant. Comparisons were made at each time point using parametric tests and over time using a linear mixed effects model. RESULTS: A total of 483 anastrozole concentration measurements, 224 samples from 64 patients on the anastrozole alone arm and 259 from 73 patients on the combination arm. The mean anastrozole concentration in the combination arm was significantly lower than that in the anastrozole alone arm at each sample collection time (all p0.01) and in the mixed effects model (an estimated difference of 9.85 ng/mL(95% CI: 5.69-14.00 ng/mL ), p0.001). CONCLUSION: A significant pharmacokinetic drug interaction was detected, in which the addition of fulvestrant to anastrozole treatment decreases the trough anastrozole concentration. Further research is needed to verify whether this interaction affects treatment efficacy and to determine the pharmacological mechanism by which this interaction occurs. This article is protected by copyright. All rights reserved.
Keywords: Breast cancer; pharmacokinetics; anastrozole; drug interaction; fulvestrant
Journal Title: British journal of clinical pharmacology
ISSN: 1365-2125; 0306-5251
Publisher: Unknown  
Date Published: 2016
Language: ENG
DOI/URL:
Notes: LR: 20160210; CI: This article is protected by copyright. All rights reserved.; JID: 7503323; OTO: NOTNLM; 2015/12/01 [received]; 2016/01/25 [revised]; 2016/02/03 [accepted]; aheadofprint