Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer

Peter C. Kohler, John T. Hamm, Valerie J. Wiebe, Michael W. DeGregorio, Irving Shemano, Douglass C. Tormey

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Toremifene is a triphenylethylene derivative structurally and pharmacologically similar to tamoxifen. This Phase I trial assessed the safety, pharmacokinetics, anti-estrogenic, and estrogenic effects of toremifene at six dose levels (10, 20, 40, 60, 200, and 400 mg/day). The most common side-effects associated with therapy included gastrointestinal (nausea/vomiting 43%), anti-estrogenic (hot flashes 29%), and CNS (dizziness/vertigo 12%). Three patients with bone metastases from breast cancer developed hypercalcemia. At doses ≥40 mg/day a decline in LH and FSH occurred which was not statistically significant. At all doses tested SHBC rose during therapy. A dose dependent estrogenic blockade was seen on the vaginal epithelium following challenge with transdermal estradiol. Steady-state concentrations of toremifene were reached within 4 weeks, and at doses ≥60 mg/day ranged from 879-3445 ng/ml. The half-life was found to be 5 days, and at three weeks following discontinuation of treatment concentrations >24 ng/ml were detected. The N-desmethyl and 4-hydroxy metabolites achieved steady state levels within 4 weeks and had half-lives of 6 and 5 days respectively. Partial responses were seen in 4 patients, 3 with breast cancer treated at 200 mg/day and 1 with endometrial cancer treated at 400 mg/day.

Original languageEnglish (US)
JournalBreast Cancer Research and Treatment
Volume16
Issue number1 Supplement
DOIs
StatePublished - Aug 1990
Externally publishedYes

Keywords

  • antiestrogens
  • pharmacokinetics
  • Phase I studies
  • tolerance
  • toremifene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Kohler, P. C., Hamm, J. T., Wiebe, V. J., DeGregorio, M. W., Shemano, I., & Tormey, D. C. (1990). Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. Breast Cancer Research and Treatment, 16(1 Supplement). https://doi.org/10.1007/BF01807140