Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A pilot study of Formestane or 4-Hydroxyandrostenedione (Lentaron), a new endocrine agent, was conducted on 18 postmenopausal patients with locally advanced and metastatic breast cancer. 16 patients were evaluable for response and objective responses were seen in 4 patients (25%). Stabilisation of disease was seen in 5 patients (32%). Out of 17 patients evaluable for toxicity, 3 (18%) reported adverse effects including hot flushes, lethargy and myalgia. Adverse effects were mild, transient and no patient required discontinuation of drug. Our study confirms that Formestane is a well tolerated endocrine agent with low toxicity and reasonable efficacy in postmenopausal patients with locally advanced and metastatic breast cancer.
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PMID:Pilot study of formestane in postmenopausal women with breast cancer. 1096 35

The use of the luteinising hormone releasing hormone (LHRH) analogues--goserelin (Zoladex, AstraZeneca) and leuprorelin (Prostap, Wyeth)--is well established and forms the backbone of the treatment of locally advanced and metastatic prostate cancer. Comparable efficacy with orchidectomy and, historically, diethylstilbestrol (DES) is accepted, with the advantages of reversibility and limited thromboembolic and cardiovascular toxicity, respectively. Side effects such as hot flushes, loss of libido, lethargy and decreased bone mineral density have recently stimulated more interest in the use of non-steroidal anti-androgens such as bicalutamide (Casodex, AstraZeneca) in locally advanced disease. Although better tolerated, bicalutamide has significant problems with gynaecomastia and breast pain. Maximal androgen blockade using LHRH analogues and their adjuvant use with radiotherapy are discussed, as well as their experimental application in intermittent androgen suppression therapy. Similar side effect profiles are reported for the LHRH analogues but injection tolerability differs with the smaller 23G needle for Prostap 3 compared to the 16G needle for Zoladex LA. There is no evidence to suggest a difference in the efficacy between the LHRH analogues goserelin and leuprorelin, although no direct comparison has yet been undertaken.
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PMID:Luteinising hormone releasing hormone analogues in the treatment of prostate cancer. 1247 66

4-Hydroxyandrost-4-ene-3,17-dione (formestane) is a selective aromatase inhibitor. It is indicated for postmenopausal patients with advanced breast cancer. The aim of the present study was to investigate the effect of 4-hydroxyandrost-4-ene-3,17-dione on the bile secretion and metabolism of 4-(14)C-cholesterol to bile acid. The experiments were carried out in the ovariectomized and sham-operated female Wistar rats. Formestane (20 mg/kg, i.m., daily) was administered to animals for 2 weeks. Twenty four hours after the last drug administration, rats were anesthetized with ethyl urethane. 4-(14)C-cholesterol (740 kBq/kg, s.a. 2.28 GBq/mmol) was infused for 1 min by catheter inserted into the jugular vein. Bile samples were assayed for total 14C radioactivity 14C-bile acids were determined in bile (after thin-layer chromatographic separation) by the use of isotopic technique with liquid scintillator. Previous studies showed that systemic adverse effects occurred in about 12% of patients following intramuscular drug administration. Many of them such as hot flushes, vaginal spotting and emotional lability were related to the mechanism of action of formestane i.e. estrogen suppression. Lethargy, rash, nausea, dizziness, indigestion, ataxia, cramps and facial swelling have also been reported. The results of the present study have shown that formestane administered to the female ovariectomized rats decreased the bile secretion and diminished conversion of 4-(14)C-cholesterol to trihydroxy bile acids. The decreased synthesis of trihydroxy bile acids and increased concentrations of cholesterol and litocholic acid in bile may be associated with increased risk of gallstone formation.
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PMID:Effect of 4-hydroxyandrost-4-ene-3,17-dione (formestane) on the bile secretion and metabolism of 4-(14)C-cholesterol to bile acids. 1638 15