Toremifene: Pharmacologic and pharmacokinetic basis of reversing multidrug resistance

M. W. DeGregorio, J. M. Ford, C. C. Benz, V. J. Wiebe

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


Triphenylethylene compounds, such as tamoxifen, have shown chemosensitizing activity independent of estrogen receptor status in doxorubicin-resistant cells. We examined the chemosensitizing activity of a new triphenylethylene, toremifene, and its major metabolites in a doxorubicin-resistant human breast cell line, MCF-7/DOX. In addition, we examined the chemosensitizing activity of unbound plasma toremifene and its metabolites isolated from patients treated with toremifene doses of 20 to 400 mg/d. MCF-7/DOX cells were exposed to ultrafiltrate plasma specimens in the absence and presence of doxorubicin. These latter studies were single-blinded. Toremifene and its major metabolites were capable of sensitizing multidrug-resistant cells to doxorubicin. The degree of chemosensitizing activity in vitro correlated with the plasma concentrations of toremifene and its metabolites (P < .05). Plasma samples isolated from patients receiving high-dose toremifene (400 mg/d) had the greatest chemosensitizing activity. We present evidence that toremifene and its metabolites can sensitize resistant MCF-7/DOX cells to doxorubicin, that this effect is concentration-dependent, and that sensitizing activity can be detected at clinically achieved concentrations.

Original languageEnglish (US)
Pages (from-to)1359-1364
Number of pages6
JournalJournal of Clinical Oncology
Issue number9
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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