[Steady state and disappearance of the metabolites of miproxifene phosphate in the treatment of breast cancer]

Gan To Kagaku Ryoho. 1998 Aug;25(10):1565-73.
[Article in Japanese]

Abstract

We gave miproxifene phosphate to six patients with recurrent breast cancer and to one patient with advanced breast cancer. This drug was orally administered at a daily dose of 20 mg in the morning, and serial blood samples were obtained just before the drug administration. Treatment was discontinued in 16 days in the patient with advanced breast cancer. Tumor response was 2 PR and 4 NC (3MR) with an efficacy rate of 29%. Adverse effects of grade 2, such as anorexia, nausea or vomiting and fatigue with grade 3 flushing and chilling were observed in the one patient with advanced breast cancer. This climacteric syndrome disappeared after cessation of administration. In one of the patients with recurrent breast cancer, a calf muscle cramp was observed. Steady plasma levels were observed in one week or two for miproxifene and in 2 to 8 weeks for desmethyl miproxifene, which were active metabolites of miproxifene phosphate. The half lives of these metabolites for disappearance were calculated in three patients. That of miproxifene was 27 to 36 hours and that of desmethyl miproxifene was 156 to 202 hours. Miproxifene phosphate is a promising drug for breast cancer, and the results of pharmacokinetics of active metabolites will suggest the time to obtain maximum efficacy and for it to disappear.

Publication types

  • English Abstract

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Estrogen Antagonists*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / metabolism
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / blood
  • Tamoxifen / metabolism

Substances

  • Antineoplastic Agents
  • Estrogen Antagonists
  • Tamoxifen
  • TAT 59
  • 2-(4-(1-(4-hydroxyphenyl)-2-(4-isopropylphenyl)-1-butenyl)phenoxy)-N,N-dimethylethylamine