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

Daniel L. Hertz, William E. Barlow, Kelley M. Kidwell, Kathy S. Albain, Ted A. Vandenberg, Shaker R. Dakhil, Nagendra R. Tirumali, Robert B. Livingston, Julie Gralow, Daniel F. Hayes, Gabriel N. Hortobagyi, Rita S. Mehta, James M. Rae

Research output: Contribution to journalArticle

10 Scopus citations

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 were included, 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 P < 0.01) and in the mixed effects model (an estimated difference of 9.85 ng ml-1 (95% CI 5.69, 14.00 ng ml-1), P < 0.001). Conclusion A significant pharmacokinetic drug interaction was detected, in which the addition of fulvestrant to anastrozole treatment decreased 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.

Original languageEnglish (US)
Pages (from-to)1134-1141
Number of pages8
JournalBritish Journal of Clinical Pharmacology
Volume81
Issue number6
DOIs
StatePublished - Jun 1 2016

Keywords

  • anastrozole
  • breast cancer
  • drug interaction
  • fulvestrant
  • pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226'. Together they form a unique fingerprint.

  • Cite this

    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. (2016). Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226. British Journal of Clinical Pharmacology, 81(6), 1134-1141. https://doi.org/10.1111/bcp.12904