Clinical potential of new antiestrogens.
OBJECTIVE
Based on the data and clinical experience derived from tamoxifen usage, the properties of an ideal antiestrogen is described that could have applications as a breast cancer preventative agent, long-term adjuvant therdpy, or as a treatment for osteoporosis. Each of the new antiestrogens currently being tested is discussed in terms of laboratory development, toxicology, pharmacology, endocrinology, and clinical evaluation. And each new compound is assessed according to the properties of an ideal antiestrogen.


METHODS
A review of all published reports was facilitated by the use of Medline computer searches.


RESULTS
Numerous compounds are being evaluated in clinical trials and can be categorized as triphenylethylenes or tamoxifen analogs, pure antiestrogens, and targeted antiestrogens. Several of these compounds may have fewer uterotropic properties and greater effects on maintaining bone density compared with tamoxifen; however, the clinical experience (ie, patient-years of treatment) with any of these compounds is minimal.


CONCLUSIONS
Although many of these compounds appear promising, further evaluation will be necessary to determine the role these compounds may serve as preventive agents, adjuvant therapies, treatments for advanced disease, or other medical indications such as osteoporosis.
Gradishar
W J
WJ
Department of Medical Oncology, Northwestern University Medical School, Chicago, IL 60611, USA.
Jordan
V C
VC
D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects; D015507:Drugs, Investigational / Q000737:chemistry / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control; D010880:Piperidines / Q000494:pharmacology; D020849:Raloxifene Hydrochloride; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D017312:Toremifene / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D015507:Drugs, Investigational; D004965:Estrogen Antagonists; D010880:Piperidines; D013629:Tamoxifen; C038345:droloxifene; C064635:TAT 59; D000077267:Fulvestrant; C071362:idoxifene; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D017312:Toremifene