Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aminoglutethimide (AG) was administered as palliative therapy in 112 patients with metastatic breast cancer. In 36 patients, the dose level was 1000 mg/day; 76 patients received a dose level of 500 mg/day. Patients with brain or liver metastasis were excluded, as were patients with tumors determined to be negative for estrogen receptors. Objective regression was observed in 35 (31%) patients, with the duration of response ranging from 4 to 36 + months (mean, 12 months; median, 10 months). Response was observed in 11 of 31 (35%) patients with soft tissue metastasis; 16/59 (27%) patients with osseous metastasis; and 8 of 22 (36%) having visceral metastasis. In 93 patients with positive estrogen receptor (ER), 33 responded (35%), whereas in 19 patients with unknown ER status, two responded (11%). Response to previous treatment with tamoxifen (TAM) had occurred in 31 patients; of these, response to AG was noted in 11 (35%). Of 24 patients failing to respond to prior treatment with tamoxifen, four (17%) responded to subsequent therapy with AG. Thirteen patients had previously received combination chemotherapy, and response to AG was noted in two (15%). The side effects observed in this study included skin rash in ten patients, fever in eight, somnolence in three, weakness and dizziness in one, headache in one, insomnia in one, dyspnea in one, and ataxia in one. Treatment had to be discontinued in eight patients, due to the severity of the side effects. As expected, patients receiving AG at the lower dose level of 500 mg/day experienced fewer and less severe side effects than those treated with the higher dose. The response rate in the 1000 mg/day group was 10/36 (28%) and in the 500 mg/day group, it was 25/76 (33%). The lower dosage was better tolerated without apparent compromise in therapeutic efficacy.
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PMID:Aminoglutethimide in patients with metastatic breast cancer. 246 35

A progress report is presented on two on-going clinical trials in women with advanced breast cancer. In Trial I to date, 56 patients have been randomized to tamoxifen (TAM) alone or TAM plus aminoglutethimide (AG) (plus hydrocortisone). Patients failing TAM can then receive AG. The two groups are reasonably well balanced with respect to prior hormonal therapy exposure (TAM, 19%; TAM plus AG, 17%), age, disease-free interval, performance score, and estrogen receptor status. The TAM plus AG group has a higher incidence of visceral dominant disease (41 versus 26%) and prior chemotherapy exposure (41 versus 33%). Responses have been observed in 7 of 27 (26%) patients on TAM and 11 of 28 (39%) on TAM plus AG. Median times to treatment failure (defined as disease progression, unacceptable toxicity, or patient refusal) are 211 and 123 days, respectively (log-rank on time to treatment failure, p = 0.87). Toxicity is greater for TAM plus AG with a higher incidence of skin rash, lethargy, and dizziness. Thrombotic events were seen in one patient on TAM and two patients on TAM plus AG. One patient on TAM plus AG developed leukopenia and sepsis. The data are too preliminary for one to draw firm conclusions regarding relative efficacy. In TRial II to date, 35 patients with prior tamoxifen exposure have received AG. The mean number of prior systemic therapies is 3.2 (range, 1 to 7). The response rate is 20% and similar with (21%) or without (19%) prior chemotherapy exposure. The median time to treatment failure is 92 days. One patient developed leukopenia and sepsis. Additional patient accrual is necessary to allow characterization of potential efficacy within prognostically important subsets.
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PMID:Progress report on two clinical trials in women with advanced breast cancer. Trial I: tamoxifen versus tamoxifen plus aminoglutethimide. Trial II: aminoglutethimide in patients with prior tamoxifen exposure. 704 29

In order to determine the usual dose in the first line therapy and a high dose in the second or third line therapy, a dose finding study of a novel antiestrogen NK 622 (toremifene citrate) was performed in patients (pts) with advanced or recurrent breast cancer. NK 622 was orally administered daily once for more than 8 weeks. In pts without previous drug therapy or in pts with cancer relapse after adjuvant therapy, the response rates [(CR + PR)/total] were 24.1% (7/29), 13.8% (4/29), 20.0% (1/5) and 40.0% (2/5) at doses of 40, 60, 120 and 240 mg/day, respectively. A 40 mg/day dose showed an objective response only in postmenopausal pts with estrogen receptor (ER) positive or unknown cancer. At a dose of 60 mg/day, some of the responding cases were premenopausal pts or pts with ER(-) cancer. In pts with cancer relapse during adjuvant therapy or in those with previous therapy and/or radiation, response rates were 25.0% (2/8), 0% (0/4), 13.5% (5/37) and 10.3% (4/39) at doses of 40, 60, 120 and 240 mg/day, respectively. Response was more frequent in pts with ER (+) cancer than with ER (-) cancer. The response rates in pts with previous therapy including tamoxifen (TAM) except medroxyprogesterone (MPA) were 14.3% (4/28) at a 120 mg/day dose and 6.1% (2/33) at a 240 mg/day dose. In pts with previous therapy including TAM, MPA and other antitumor agents, the rate was 18.2% (2/11) at a 120 mg/day dose. Side effects such as elevation of GOT, GPT and serum Ca level, decrease of hemoglobin, anorexia, nausea/vomiting, fatigue, dizziness and hot flush were observed. These side effects were moderate in grade and reversible. Dose dependency of side effects was not clearly observed in grade and incidence. From these results, NK 622 is expected to be a safe drug with efficacy in first line therapy at a dose of 40 mg/day and in second or third line therapy at a dose of 120 mg/day.
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PMID:[Phase II study of NK 622 (toremifene citrate) in advanced breast cancer, a multicentral cooperative dose finding study]. 842 89

The triphenylethylene antiestrogen toremifene is a chlorinated derivative of the antiestrogen tamoxifen, an agent which has been widely and successfully used in the treatment of breast cancer. Clinical trials investigating the efficacy of toremifene as first-line endocrine therapy in postmenopausal women with advanced breast cancer (estrogen receptor status positive or unknown) have shown this drug to have similar antitumour activity to that of tamoxifen. In multicentre comparative trials, objective responses (complete and partial) occurred in 20 to 29% of patients treated with toremifene (60 to 240 mg/day) and in 19 to 37.5% of tamoxifen (20 or 40 mg/day) recipients. The duration of response, time to disease progression and median overall survival time were generally similar in both treatment groups. Toremifene is well tolerated. Most drug-related adverse effects are mild or moderate in severity and rarely necessitate discontinuation of therapy. The tolerability profile of toremifene is similar to that reported for tamoxifen, the most common adverse effects being hot flushes, sweating, nausea and/or vomiting, dizziness, oedema, and vaginal discharge and/or bleeding. Thus, toremifene provides an equally effective and well tolerated alternative to tamoxifen for the first-line endocrine therapy of postmenopausal advanced breast cancer. Preclinical studies showing toremifene to have a lower carcinogenic potential than tamoxifen indicate that toremifene may be a preferable agent for long term treatment regimens; however, these findings require confirmation in the clinical setting.
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PMID:Toremifene. A review of its pharmacological properties and clinical efficacy in the management of advanced breast cancer. 921 Oct 86

Exemestane is an irreversible, steroidal, oral aromatase inhibitor under evaluation in postmenopausal women with advanced breast cancer. A phase I study was conducted in 27 postmenopausal patients who were candidates for hormone therapy because they had advanced breast cancer and estrogen receptor-positive or unknown status. Most patients were moderately or heavily pretreated. Cohorts of at least three patients received sequentially escalating daily oral doses of 5-600 mg. The median duration of exemestane treatment was 13 weeks (range: 3-166 weeks). The maximal tolerated dose was not reached because of lack of treatment-related grade 3 or 4 toxicity. The most common adverse events, including those not related to treatment, were mild to moderate headache (44% of patients), dizziness (33%), nausea (33%), hot flushes (30%) and tumor-related pain (30%). There were three complete and four partial responses for an objective response rate of 26% (95% CI: 11.1-46.3%) in the intent-to-treat population; the median duration of response was 74 weeks (95% CI: 48-99 weeks). Exemestane, at the dose of 25 mg, maximally suppressed estradiol, estrone and estrone sulfate serum levels to 13, 5 and 10% of baseline, respectively. Exemestane appears to suppress estrogen, be well tolerated and have antitumor activity in postmenopausal women with advanced breast cancer. A large, safe therapeutic window of up to 600 mg was defined. In view of its safety and estrogen-suppression profiles, the most favorable effects were observed at the 25 mg daily dose.
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PMID:Safety, activity and estrogen inhibition by exemestane in postmenopausal women with advanced breast cancer: a phase I study. 982 25

In every year since 1984, cardiovascular disease has claimed the lives of more females than males. More than 450,000 women succumb to heart disease annually, and 250,000 die of coronary artery disease. Despite the proportions, most women believe they will die of breast cancer. The perception that heart disease is a man's disease and that women are more likely to die of breast cancer is alarming. Although women develop heart disease about 10 years later than men, they are likely to fare worse after a heart attack. The poorer outcomes are due, in part, to the failure to identify heart attack symptoms. Approximately 35% of heart attacks in women are believed to go unnoticed or unreported. However, because of increased age, women are more likely to have co-morbid diseases such as diabetes and hypertension. In women, not only is "tightness" or discomfort in the chest a warning sign, but in addition, nausea and dizziness are common indicators of myocardial ischemia. Other symptoms include breathlessness, perspiration, a sensation of fluttering in the heart, and fullness in the chest. In comparison to men, women are less likely to undergo tertiary care interventions such as cardiac catheterization, angioplasty, thrombolytic therapy, and bypass surgery; to participate in cardiac rehabilitation; and to return to work full-time after myocardial infarction. In the past, most research about treatments for heart disease focused on men, and gender differences have been ignored. Recent studies are enrolling enough women to test if there are differences between men and women in outcomes. One of the major areas of research relates to estrogen and hormonal replacement therapy to reduce the relative risk of heart attack and stroke. The Women's Health Initiative is a major NIH-sponsored trial that addresses the issue of primary prevention of cardiac disease by hormonal replacement therapy. The results will be available in 2004. The Heart Estrogen/Progestin Replacement Study (HERS), disappointingly, did not show a significant reduction of coronary events in women taking hormonal replacement therapy, nor did the Estrogen Replacement and Atherosclerosis (ERA) trial of 309 postmenopausal women who underwent coronary angiography. New insight into the role of vitamins, phytoestrogens and other natural sources, and selective estrogen receptor modulators may provide other options for management. Until then, modification of risk factors and healthy life style choices are recommended for reducing the risk of cardiac disease. In fact, the key to a healthy heart in the year 2000 appears closely tied to life style choices. Prevention of disease is the key, and current recommendations are simply to stop smoking, or do not start; treat and control blood pressure >140/90 mm Hg; manage elevated lipids by diet, exercise, and cholesterol-lowering medications (if necessary); treat diabetes; lose weight so that BMI is <25; walk for 20-30 minutes at least three times a week; and take an aspirin tablet daily.
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PMID:Heart disease in women. 1114 May 44

Raloxifene, a selective estrogen receptor modulator (SERM) licensed for the prevention of non-traumatic vertebral fractures in postmenopausal women at increased risk of osteoporosis, was launched in the UK in August 1998. The aim of the study was to monitor the safety of raloxifene prescribed in the primary care setting in England using prescription-event monitoring (PEM). Patients were identified by means of prescription data supplied by the Prescription Pricing Authority between September 1998 and November 2000. Demographic and clinical event data were collected from questionnaires posted to primary care physicians (GPs) at least 6 months after the date of the first prescription for each patient. Information on medical events, suspected adverse drug reactions (ADRs), reasons for stopping treatment, pregnancies, and causes of death was requested. Event rates [Incidence Densities (IDs): no. first reports /1000 patient-months of treatment] were calculated. Differences between IDs for events reported in month one (ID(1)) and months 2-6 (ID(2-6)) of treatment were examined. The cohort comprised 13,987 patients [median age 62 years (IQR 55,69); 99.8% female]. The major indication was osteoporosis (40.9%, n=5725). Flushing was the event with the highest ID in month 1 (22.8), reported most frequently by GPs as an ADR to raloxifene (67/461 reports) and as the reason for stopping (700/4592 reports). Events associated with starting treatment included flushing, malaise/lassitude, headache/migraine, nausea/vomiting, sweating, cramp, pain abdomen, dizziness, diarrhea, mastalgia and vaginal hemorrhage. Less common events reported during treatment included deep vein thrombosis (n=13), pulmonary embolism (n=13), thrombophlebitis (n=31) and visual disturbance (n=29). In this study, there were 122 (0.9%) confirmed deaths, of which 32 causes of death were unknown. This study shows that raloxifene is generally well tolerated when used in general practice in England. Potential signals of unrecognised ADRs requiring further evaluation included gastrointestinal adverse symptoms and vaginal hemorrhage. There were also a small number of reports of events associated with venous thromboembolism and visual disorders that require further investigation.
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PMID:Safety profile of raloxifene as used in general practice in England: results of a prescription-event monitoring study. 1530 82

The occurrence of vasomotor symptoms in women is directly related to deficiency of estrogen, which occurs as a result of natural or surgical menopause. Hot flushes may also be a major problem for patients with a history of breast cancer, as they may result directly from cancer treatment (oophorectomy, chemotherapy-induced ovarian failure or adjuvant tamoxifen citrate therapy). Despite the lack of reliable data regarding their efficacy and safety, in recent years the usage of herbs among menopausal women has increased dynamically all over the world. The following paper reviews professional literature about Black Cohosh (Actaea/Cimicifuga racemosa), either used alone or in combination with other medicinal herbs administered in management of vasomotor symptoms. Extracts of the rootstock of Black cohosh contain such potentially biologically active constituents as triterpene glycosides (actein, cimicifugoside, deoxyacetein), isoferulic acid and alkaloids (n-methylcytisine). The mechanism of its action remains unclear. Some authors suggest that Black Cohosh contains substances with selective estrogen receptor modulator (SERM) activity. Recent data has demonstrated that Black Cohosh may have an effect on dopaminergic and serotoninergic systems. Thirty-two papers formed the basis for this review. Open-label, noncomparative studies, as well as treatment-controlled, randomized, open trials, have proven that Black Cohosh significantly reduced frequency or severity of hot flashes. The results of randomized, placebo-controlled, double-blind clinical trials were contradictory. Adverse symptoms have been rare (5,4%), mild and reversible. Most of them included gastrointestinal upsets, rashes, headaches, dizziness and mastalgia. Nevertheless, single cases of serious adverse events, including acute hepatocellular damage, have been reported, but without a clear causality relationship.
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PMID:[Efficacy and safety of Black cohosh (Actaea/Cimicifuga racemosa) in the treatment of vasomotor symptoms--review of clinical trials]. 1859 68

The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions and drug-drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug-drug interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits of treatment itself, i.e., the prevention of osteoporotic fracture.
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PMID:Adverse reactions and drug-drug interactions in the management of women with postmenopausal osteoporosis. 2163 97

Treatments for postmenopausal osteoporosis are generally safe, but are linked to some rare serious adverse drug reactions, for which causality is not always certain. The bisphosphonates are associated with gastrointestinal effects, acute phase reactions, and musculoskeletal pain, and, more rarely, cases of atrial fibrillation, subtrochanteric fracture, osteonecrosis of the jaw, cutaneous hypersensitivity reactions and renal impairment. It is too soon for pharmacovigilance data on denosumab, but it has been associated with cutaneous effects and possibly osteonecrosis of the jaw (to date, only in metastatic cancer). The selective estrogen receptor modulators may induce hot flushes and leg cramps, and--more rarely--venous thromboembolism and stroke. Strontium ranelate is associated with headache, nausea and diarrhea, and, more rarely, cutaneous hypersensitivity reactions and venous thromboembolism, while teriparatide and parathyroid hormone(1-84) are associated with headache, nausea, dizziness and limb pain. The management of osteoporosis should entail weighing the probability of adverse reactions against the benefits of therapy--that is, reduction of fracture risk.
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PMID:Adverse drug reactions to osteoporosis treatments. 2222 Mar 6


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