tat-59 and droloxifene

During recent years the development of hormone therapy for the treatment breast neoplasms has seen, in addition to classic aspecific antiestrogens (AE) like tamoxifen (TAM) and to a lesser extent toremifen, a major development of new molecules divided into two groups: the first is the so-called selective estrogen receptor modulators (SERMs), the most important of which is Raloxifen, which mediate estrogen-agonist effects in some tissues and estrogen-antagonist effects in others; the second group includes the aromatase inhibitors (AI), important enzymes for peripheral estrogen conversion. Some studies compare or associate classic AE with the new SERMs and AI, both in adjuvant therapy and in treatment for advanced forms. Other trials assess the anti-osteoporotic activity of some SERMs which present concomitant inhibitory activity on the breast and endometrium.

Topics: Adult; Anastrozole; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Enzyme Inhibitors; Estrogen Antagonists; Female; Forecasting; Humans; Indoles; Letrozole; Middle Aged; Neoplasm Metastasis; Nitriles; Osteoporosis; Postmenopause; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Tamoxifen; Toremifene; Triazoles

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

Topics: Antineoplastic Agents, Hormonal; Bone Density; Drugs, Investigational; Estradiol; Estrogen Antagonists; Female; Fulvestrant; Humans; Osteoporosis, Postmenopausal; Piperidines; Raloxifene Hydrochloride; Tamoxifen; Toremifene

Tamoxifen (20-40 mg/day) has been widely used for the treatment of breast cancer and is recognized as a useful antiestrogen. A 40 mg/day dose of toremifene showed comparable efficacy, safety and usefulness to a 20 mg/day dose of tamoxifen in the double-blind comparative study with tamoxifen. Furthermore, high-dose toremifene (120 mg/day) was effective on the tamoxifen-failed breast cancer patients. Although droloxifene (3-hydroxytamoxifen) showed efficacy and safety in phase I and phase II studies, this trial has regretably been ineffective in Japan. In phase I and early phase II trials in Japan, the safety and efficacy of TAT-59 was demonstrated and a 20 mg/day dose was moderate. Tamoxifen analogues including their metabolites are expected to act effectively on tamoxifen-resistant, low estrogen receptor levels or estrogen receptor-negative tumors by mechanisms of action different from tamoxifen.

Topics: Binding, Competitive; Breast Neoplasms; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Receptors, Estrogen; Tamoxifen; Toremifene