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)

In a European multicentre phase II study, 80 postmenopausal patients (pts) with advanced breast cancer progressing on aminoglutethimide (AG) at daily doses of > or = 500 mg were enrolled. Seventy-eight received exemestane (200 mg daily orally), including 33 pts resistant to prior AG, 39 pts who had progressed after an initial response to AG, and 6 pts whose response to AG was either unavailable or not evaluable. Three pts were pretreated with AG only, 69 with tamoxifen and AG, and 6 with tamoxifen, AG and other hormone therapies; 55% had also previously received chemotherapy. The predominant site of disease was visceral in 34 cases, bone in 27 and soft tissue in 17. Based on Peer Review assessment, the overall objective response rate (CRs plus PRs) was 26% (12% in pts resistant to AG and 33% in AG-responsive pts). Disease stabilisation > or = 24 weeks was achieved in an additional 13% of patients (15% of those resistant to AG and 13% of those AG-responsive), resulting in an overall success rate of 39% (28-50, 95% confidence interval). The median duration of objective response, overall success and median TTP were 59, 48 and 21 weeks, respectively. Toxicities were usually mild to moderate in severity, with hot flushes (21%), nausea (19%), dizziness (12%), weakness (12%), increased sweating (12%), androgenic symptoms (10%) and peripheral oedema (9%) as the most common side-effects. Only 2 pts (3%) discontinued treatment due to adverse events. These results are very promising considering that exemestane was administered as third- or fourth-line hormonal treatment in most cases and confirm previous observations about the lack of cross-resistance when steroidal aromatase inhibitors are sequenced with the non-steroidal aromatase inhibitor AG.
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PMID:Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on aminoglutethimide: a phase II multicentre multinational study. Exemestane Study Group. 947 Aug 30

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

To elucidate the combined effects of fadrozole (nonsteroidal aromatase inhibitor) and tamoxifen, 11 postmenopausal patients with recurrent breast cancer were examined between October 1996 and June 1998. One patient, 49 years old, was ineligible due to the short period after castration. The patients were aged 53-71 years (mean 63.5). PS was 0-1. Six patients were pre-treated with tamoxifen and 6 with oral 5-FU derivatives. One had no previous treatment. The target lesions were soft tissues in 5, bone in 4, lungs in 6 and liver in 1. The response was CR in 2, PR in 2, SD (longer than 24 weeks) in 2, NC in 1 and PD in 3. Consequently, the response rate was 60% (6 out of 10 eligible cases). Hormonal concentration was measured before and after administration of two drugs in weeks 2, 4, 6, 8 and at the end of the treatment, and significant decreases in estrogens in peripheral blood were observed. Adverse effects (4 cases of low grade headache, dizziness and elevation of GOT, GPT, gamma-GTP) did not influence the continuous administration of the drugs. We conclude that combined administration of fadrozole (2nd generation aromatase inhibitor) and tamoxifen produces a good response in postmenopausal recurrent breast cancer patients, and can be a useful treatment for patients with breast cancer.
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PMID:[A combined effect of fadrozole and tamoxifen in postmenopausal patients with recurrent breast cancer: a preliminary report: Japanese Cooperative Study Group of Fadrozole and Tamoxifen]. 1105 22

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

The impact of treatment on health-related quality of life (HRQoL) is an important consideration in the adjuvant treatment of operable breast cancer. Here we report mature HRQoL outcomes from the ATAC trial, comparing anastrozole with tamoxifen as primary adjuvant therapy for postmenopausal women with localized breast cancer. Patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire plus endocrine subscale (ES) at baseline, 3 and 6 months, and every 6 months thereafter. Baseline characteristics in the HRQoL sub-protocol were well balanced between the anastrozole (n = 335) and tamoxifen (n = 347) groups in the primary analysis population. As with previously published results at 2 years, there was no statistically significant difference in the Trial Outcome Index of the FACT-B, the primary endpoint of the study, between treatments at 5 years. There were no statistically significant differences between treatment groups in ES total scores. Consistent with the 2-year analysis, there were differences between treatment groups in patient-reported side effects: diarrhea (anastrozole 3.1% vs. tamoxifen 1.3%), vaginal dryness (18.5% vs. 9.1%), diminished libido (34.0% vs. 26.1%), and dyspareunia (17.3% vs. 8.1%) were significantly more frequent with anastrozole compared to tamoxifen. Dizziness (3.1% vs. 5.4%) and vaginal discharge (1.2% vs. 5.2%) were significantly less frequent with anastrozole compared to tamoxifen. In this, the first report of HRQoL over 5 years of initial adjuvant therapy with an aromatase inhibitor, we conclude that anastrozole and tamoxifen had similar impacts on HRQoL, which was maintained or slightly improved during the treatment period for both groups.
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PMID:Quality of life of postmenopausal women in the ATAC ("Arimidex", tamoxifen, alone or in combination) trial after completion of 5 years' adjuvant treatment for early breast cancer. 1694 95