Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004093 (asthenia)
 2,650 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of anastrozole, a new selective aromatase inhibitor, in treating hormone-responsive metastatic breast cancer is discussed. Treatment options for hormone-dependent breast cancer focus on interfering with the endocrine system in an attempt to modify the effects of estrogen. Tamoxifen is the drug of choice for primary endocrine therapy, but there is a need for agents with similar or greater efficacy and better tolerability. Anastrozole inhibits the conversion of androgens to estrogens by aromatase. Bioavailability studies have demonstrated almost complete absorption of anastrozole after oral administration. The drug's terminal half-life after multiple doses is 50 hours. Anastrozole is cleared principally by the liver. Clinical trials comparing anastrozole with megestrol acetate demonstrated no significant differences in clinical efficacy, although a follow-up study revealed a longer median overall survival rate in patients receiving anastrozole. The drug is well tolerated. Among the most frequently reported adverse effects are asthenia, hot flashes, headache, and back pain. The recommended dosage is 1 mg daily. The average wholesale cost of month's supply of anastrozole is $187.20, compared with approximately $100 for generic megestrol acetate or aminoglutethimide plus hydrocortisone. Although anastrozole will likely become the preferred second-line agent in the treatment of postmenopausal breast cancer in patients with disease progression after tamoxifen therapy, it is not a therapeutic alternative to aminoglutethimide on the basis of approved indications. Anastrozole and other aromatase inhibitors may have multiple applications in treating hormone-responsive breast cancer.
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PMID:Anastrozole: a selective aromatase inhibitor for the treatment of breast cancer. 952 27

Third-generation aromatase inhibitors are able to reduce circulating plasma estrogen concentrations in postmenopausal women to below detectable limits and significantly inhibit aromatase, the enzyme responsible for estrogen synthesis, in normal breast tissue and breast tumors. Their role in the treatment of advanced breast cancer is well established and their use in adjuvant therapy is currently being explored. On the basis of these trials, evaluation of these inhibitors in the prevention of breast cancer may be appropriate. Aromatase inhibitors have non-specific toxic side effects including (but not limited to): asthenia, headache, nausea, peripheral edema, fatigue, vomiting and dyspepsia. In addition, certain endocrinological side effects in postmenopausal women are notable, namely hot flushes and vaginal dryness. In advanced breast cancer, these side effects result in treatment withdrawal in few (<4%) women. Of concern, however, are the potential long-term endocrinological side effects in women receiving treatment as first-line adjuvant therapy or in sequence or combination with tamoxifen or other selective estrogen receptor modulators (SERMs). Current studies of adjuvant treatments for breast cancer in healthy women are carefully evaluating, in addition to general toxicities, the effects on bone, lipid metabolism, cardiovascular risk, quality of life and menopausal symptoms. Careful evaluation of all-cause morbidity and mortality is necessary to plan trials and justify long-term use of aromatase inhibitors in the treatment or prevention of breast cancer in healthy women.
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PMID:Risks versus benefits in the clinical application of aromatase inhibitors. 1073 Nov 26

Fulvestrant (Faslodex) is a novel estrogen receptor (ER) antagonist that competitively binds to the ER with a much greater affinity than that of tamoxifen. The downregulation of cellular levels of the ER protein results in complete abrogation of estrogen-sensitive gene transcription. This distinct mechanism of action ensures a lack of cross resistance with other hormonal agents and, in contrast to tamoxifen, fulvestrant has no known estrogen-agonist effects. Fulvestrant is administered via monthly intramuscular injections (250mg) and is recommended for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. The efficacy of fulvestrant was similar to that of the aromatase inhibitor anastrozole (1 mg/day) in two, well designed studies in postmenopausal women with locally advanced or metastatic breast cancer that had progressed during prior antiestrogen therapy. Time to disease progression (primary endpoint) and treatment failure, rates of objective response and clinical benefit, overall survival and quality of life were similar in patients treated with fulvestrant or anastrozole. In retrospective noninferiority analyses, fulvestrant was at least as effective as anastrozole in all randomised patients, and in those with or without visceral metastases. Fulvestrant is generally well tolerated and was tolerated as well as anastrozole in clinical trials. Treatment-related adverse events were mostly mild to moderate and led to treatment withdrawal in about 1% of patients who received fulvestrant or anastrozole. The main adverse effects associated with therapy are nausea, asthenia, pain, vasodilation and headache.In conclusion, monthly intramuscular injections of fulvestrant are at least as effective and as well tolerated as oral anastrozole once daily in the treatment of postmenopausal women with advanced breast cancer that has progressed on prior antiestrogen therapy. Because of a different mode of action to that of other hormonal agents, fulvestrant is effective in the treatment of tamoxifen-resistant disease and, unlike tamoxifen, has no known estrogen agonist effects. Thus, fulvestrant provides an effective and well tolerated option for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
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PMID:Fulvestrant: a review of its use in hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. 1501 96