Pharmacokinetics, Pharmacological and Anti-Tumour Effects of the Specific Anti-Oestrogen ICI 182780 in Women With Advanced Breast Cancer

Br J Cancer. 1996 Jul;74(2):300-8. doi: 10.1038/bjc.1996.357.


We have assessed the pharmacokinetics, pharmacological and anti-tumour effects of the specific steroidal anti-oestrogen ICI 182780 in 19 patients with advanced breast cancer resistant to tamoxifen. The agent was administered as a monthly depot intramuscular injection. Peak levels of ICI 182780 occurred a median of 8-9 days after dosing and then declined but were above the projected therapeutic threshold at day 28. Cmax during the first month was 10.5 ng/ml-1 and during the sixth month was 12.6 ng ml-1. The AUCs were 140.5 and 206.8 ng day ml-1 on the first and sixth month of dosing respectively, suggesting some drug accumulation. Luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels rose after withdrawal of tamoxifen and then plateaued, suggesting no effect of ICI 182780 on the pituitary-hypothalamic axis. There were no significant changes in serum levels of prolactin, sex hormone-binding globulin (SHBG) or lipids. Side-effects were infrequent. Hot-flushes and sweats were not induced and there was no apparent effect of treatment upon the endometrium or vagina. Thirteen (69%) patients responded (seven had partial responses and six showed "no change' responses) to ICI 182780, after progression on tamoxifen, for a median duration of 25 months. Thus ICI 182780, given by monthly depot injection, and at the drug levels described, is an active second-line anti-oestrogen without apparent negative effects on the liver, brain or genital tract and warrants further evaluation in patients with advanced breast cancer.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Drug Resistance, Neoplasm
  • Estradiol / adverse effects
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacokinetics
  • Estradiol / pharmacology
  • Estrogen Antagonists / adverse effects
  • Estrogen Antagonists / pharmacokinetics*
  • Estrogen Antagonists / pharmacology*
  • Female
  • Follicle Stimulating Hormone / blood
  • Fulvestrant
  • Humans
  • Luteinizing Hormone / blood
  • Middle Aged
  • Sex Hormone-Binding Globulin / metabolism


  • Antineoplastic Agents
  • Estrogen Antagonists
  • Sex Hormone-Binding Globulin
  • Fulvestrant
  • Estradiol
  • Luteinizing Hormone
  • Follicle Stimulating Hormone