Endocrine mechanism of action of toremifene at the level of the central nervous system in advanced breast cancer patients |
| |
Authors: | Irene Számel Iván Hindy Barna Budai Lauri Kangas Alajos Hajba Risto Lammintausta |
| |
Institution: | (1) Clinical Research Department, National Institute of Oncology, P.O. Box 21, H-1525 Budapest, Hungary Tel.: (36)-1-1554 411; Fax: (36)-1-2248620, HU;(2) Research and Development International, Orion Corporation/Orion Pharma, P.O. Box 425, FIN-20101 Turku, Finland, FI |
| |
Abstract: | Purpose: To differentiate the antagonistic and agonistic effect of toremifene at the level of the hypothalamus-hypophysis axis a
leutinizing hormone-releasing hormone (LHRH) test was performed during a phase II clinical trial. Methods: In 15 postmenopausal patients with advanced breast cancer, follicle-stimulating hormone (FSH) and LH release – induced by
an LHRH agonist (Suprefact injection, 0.5 mg s.c.) – was monitored during a 16-week period of toremifene treatment (60 mg/day
p.o.). Prolactin, estradiol, and sex hormone-binding globulin (SHBG) levels were also measured. The functional test was carried
out prior to toremifene therapy and then 4, 8, 12, and 16 weeks afterward. Results: The drug sensitized the pituitary to the action of the gonadotrophins; the LHRH-induced FSH and LH release showed a considerably
increasing tendency during the toremifene therapy. Estradiol levels decreased statistically significantly and SHBG levels
showed a statistically significant increase. A decreased level of prolactin is the sign of an antiestrogenic effect of toremifene
on the hypophysis and, as a result, provides evidence for a direct influence of toremifene upon the pituitary. An increase
in LH and prolactin release in response to the LHRH test was characteristic in the responders. Conclusion: According to the LHRH test, the antagonistic effect of toremifene seems to be more dominant than the concomitantly existing
agonistic property. Neither clinical nor endocrinological side effects could be observed at the level of the CNS during a
prolonged period of toremifene administration.
Received: 13 July 1997 / Accepted: 17 February 1998 |
| |
Keywords: | Breast cancer Antiestrogens Toremifene LHRH test Sex hormones |
本文献已被 SpringerLink 等数据库收录! |
|