Cancer Chemotherapy and Pharmacology

, Volume 31, Issue 5, pp 412–414

Targeting chemosensitizing doses of toremifene based on protein binding

  • Gregory T. Wurz
  • Vernon D. Emshoff
  • Michael W. DeGregorio
  • Valerie J. Wiebe
Short Communication Multidrug Resistance, Toremifene, Protein Binding

DOI: 10.1007/BF00686157

Cite this article as:
Wurz, G.T., Emshoff, V.D., DeGregorio, M.W. et al. Cancer Chemother. Pharmacol. (1993) 31: 412. doi:10.1007/BF00686157

Summary

Toremifene is currently being evaluated as a chemosensitizing agent in doxorubicin-resistant patients. Although concentrations of >2 μM reverse resistance in vitro, target concentrations required to reverse multidrug resistance (MDR) in vivo may be highly influenced by variables such as protein binding in serum. We examined the effects of high serum concentrations on the cellular accumulation of toremifene in an MDR MDA-MB-A-1 human breast-cancer cell line. We then examined the cellular accumulation of doxorubicin at various toremifene concentrations in 5%–100% serum. We also measured the concentrations of toremifene and its major metabolites in plasma specimens obtained from two patients receiving 360 mg/day for 5 days in a phase I study. Our results show that (1) high serum concentrations decrease toremifene accumulation, (2) toremifene concentrations of ≥2.5 μm enhance doxorubicin accumulation, and (3) patients achieve plasma toremifene concentrations of 10–15 μm following doses of 360 mg/day×5 days. Our findings suggest that in vivo toremifene concentrations well above those used to reverse resistance in vitro are required to overcome the effect of high serum-protein binding.

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Gregory T. Wurz
    • 1
  • Vernon D. Emshoff
    • 1
  • Michael W. DeGregorio
    • 1
  • Valerie J. Wiebe
    • 1
  1. 1.Department of Medicine, Division of OncologyThe University of Texas Health Science CenterSan AntonioUSA

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