Therapeutic significance and the mechanism of action of the LH-RH agonist ICI 118630 in breast and prostate cancer.
The influence of the LH-RH agonist ICI 118630 on circulating levels of the pituitary gonadotrophins LH and FSH and the gonadal steroids oestradiol, progesterone, 17-hydroxyprogesterone and testosterone has been studied in phase I clinical trials of the drug in patients with advanced breast or prostate cancer. ICI 118630 initially stimulated plasma levels of LH and FSH. On continued treatment however, the drug reversed this response and produced a rapid decline in plasma testosterone and progesterone in male and female patients respectively. Plasma oestradiol concentrations equivalent to those seen in oophorectomised or postmenopausal women were eventually produced in all 5 female patients treated with ICI 118630. In one patient however persistent follicular activity occurred until her third menstrual cycle. No appreciable side effects of the drug were observed. These data indicate that ICI 118630 initiates a castration-like endocrine response and has potential in the treatment of hormone dependent tumours of the breast and prostate.
D001943:Breast Neoplasms / Q000188:drug therapy*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017273:Goserelin; D006801:Humans; D006908:Hydroxyprogesterones / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011374:Progesterone / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D006908:Hydroxyprogesterones; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone