Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of long-term administration of leuprorelin acetate depot (TAP-144-SR), a sustained-release preparation of luteinising hormone-releasing hormone (LH-RH) agonist, to 40 stage D prostate cancer patients who had had no previous hormonal therapy, have been analyzed. The drug was administered by subcutaneous injection once every four weeks at a dose of 3.75 or 7.5 mg. The mean duration of treatment was 480 (141-1,266) days, and treatment continued for more than one year for 60% of the 40 patients. Objective response was evaluated in accordance with Japanese Response Criteria. The best objective response in the overall evaluation was a partial response in 68.6% of the total patient group (3.75 mg, 64.3%; 7.5 mg, 71.4%). During the administration period, 21 patients were diagnosed as having progressive disease (PD), and the mean time to onset of PD was 308 days. The earliest diagnoses of PD were made on bone metastases (17 cases) and prostatic acid phosphatase levels (12 cases). The survival rate, as determined by Kaplan-Meier's method, was 81.2% (3.75 mg, 80.5%; 7.5 mg, 81.3%) two years after starting the regimen and 66.0% (3.75 mg, 65.1%; 7.5 mg, 66.0%) after three years. There was no dose dependency between either of the two drug doses, which we adopted as functions of the objective response rate, and patients' survival. Serum levels of testosterone, LH and follicle-stimulating hormone (FSH) were monitored from the first-dose until the 148th week of administration. In all patients receiving the drug as scheduled, the testosterone level was maintained at less than 1 ng/ml, and the LH and FSH levels were maintained at levels lower than their respective upper normal limits. There were no particular adverse reactions specific to the long-term administration subsequent to the foregoing 12-week administration study. In conclusion, LH-RH analogue treatment is thought to be a long-lasting, effective, palliative measure for patients with previously-untreated, advanced, prostatic cancer.
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PMID:Long-term clinical study on luteinising hormone-releasing hormone agonist depot formulation in the treatment of stage D prostatic cancer. The TAP-144-SR Study Group. 151 66

Toremifene is a chlorinated tamoxifen analogue that is indicated for the treatment of postmenopausal hormone-dependent breast cancer. It competes with estradiol for estrogen receptors and has growth-inhibitory effects on MCF-7 breast cancer cells. At concentrations < 10(-6) mol/L, this growth inhibition can be reversed by estradiol, but at higher concentrations toremifene is cytotoxic. In dimethylbenzanthracene (DMBA)-induced mammary cancer in rats, toremifene has been shown to decrease the number of new tumours and to inhibit the growth of existing tumours. Toremifene causes growth inhibition by suppressing mitosis and inducing apoptosis. The mechanism by which these events occur may involve the induction of transforming growth factor-beta 1 and inhibition of insulin-like growth factor-1 (mecasermin). Toremifene is primarily an antiestrogen, but it has some estrogen agonist properties in postmenopausal women. The latter are reflected by the fall in luteinising hormone and follicle-stimulating hormone levels and the rise in sex hormone-binding globulin levels that are associated with its use in most women. After estrogen priming, toremifene 68mg administered orally has been found to exert a similar antiestrogenic effect on the vaginal epithelium in postmenopausal women as tamoxifen 60mg. The half-life of toremifene in plasma is 5 days, and the drug is > 99% bound to plasma proteins. The main metabolites of toremifene are N-demethyl-toremifene and deaminohydroxy-toremifene. Altered liver, but not kidney, function affects the pharmacokinetics of toremifene. Toremifene 60mg daily is as effective as tamoxifen 20mg daily in the treatment of postmenopausal hormone-dependent breast cancer, producing a response in about 50% of patients. Soft tissue and visceral metastases respond better to toremifene than bone metastases. Most of the adverse effects of toremifene are related to its activity at estrogen receptors and include hot flashes, vaginal discharge and nausea. Although toremifene decreases antithrombin III levels slightly, the incidence of thromboembolic complications is low. Thus far, no carcinogenic effects have been noted in humans, and preclinical data are mostly reassuring. Toremifene has favourable effects on serum lipids, and thus has potential in preventing coronary heart disease. Although toremifene is somewhat more expensive to use than tamoxifen, toremifene is an effective and well tolerated alternative to tamoxifen in the treatment of postmenopausal women with hormone-dependent breast cancer. No formal pharmacoeconomic comparisons of toremifene and tamoxifen have yet been published. Toremifene is potentially safer than tamoxifen in relation to carcinogenic effects and effects on serum lipids.
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PMID:Toremifene in postmenopausal breast cancer. Efficacy, safety and cost. 934 56