Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The androstenedione derivative, exemestane (FCE 24304), is a new orally active irreversible aromatase inhibitor. Fifty-six post-menopausal advanced breast cancer patients entered this study to evaluate the activity of four low exemestane doses in reducing oestrogen levels. The drug's tolerability and clinical efficacy were also assessed. Exemestane was orally administered to four consecutive groups at daily doses of 25, 12.5, 5 and 2.5 mg, and the changes in oestrogen, gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate levels were evaluated. Drug selectivity was studied by measuring 17-hydroxycorticosteroid urinary levels. After 7 days of treatment, mean oestrone and oestradiol levels had decreased by respectively 64% and 65% (a decrease which was maintained over time); in the 2.5 mg group, oestrone sulphate levels also decreased by 74%. Gonadotrophin levels were significantly higher, whereas no changes in the other serum hormone levels or any interference with adrenal synthesis were detected. Treatment tolerability was satisfactory: nausea and dyspepsia were reported in 16% of patients. The overall objective response rate was 18%. In conclusion, exemestane is effective in reducing oestrogen levels at all of the tested doses and shows interesting clinical activity.
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PMID:Endocrinological and clinical evaluation of exemestane, a new steroidal aromatase inhibitor. 754 12

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

Exemestane is a steroidal agent which causes inactivation of the aromatase enzyme by binding irreversibly to the substrate binding site. Oral exemestane 25 mg/day inactivates peripheral aromatase activity (approximately 98% inactivation) and reduces basal plasma estrone, estradiol and estrone sulphate levels by 85 to 95% in postmenopausal women with advanced breast cancer. Phase II trials indicate that oral exemestane 25 mg/day is an effective second- or third-line agent in the treatment of postmenopausal women with advanced breast cancer (achieving an objective response in up to 28 and 26% of patients, respectively). Results from a phase III trial indicate that exemestane achieves a similar objective response rate to megestrol as a second-line therapy; however, exemestane achieved a significantly longer duration of overall success, time to disease progression and survival time. Exemestane is at least as well tolerated as megestrol, but is associated with significantly fewer bodyweight changes, mainly bodyweight gain (> or = 10%). Other common adverse events are hot flushes, nausea and fatigue.
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PMID:Exemestane. 1055 37

This phase II, multicentre, open-label, clinical trial evaluated antitumoral efficacy, tolerability and endocrine effects following 25 mg of treatment with oral exemestane given daily to postmenopausal women with metastatic breast cancer. Eligibility criteria included oestrogen and/or progesterone positivity or a prior response to hormonal therapy if receptor status was unknown; prior failure to tamoxifen therapy; and progressive disease. Patients were divided into three strata: patients who did not respond to tamoxifen or progressed after disease stabilisation (SD) for less than 6 months (stratum 1); patients who, after an initial response or SD lasting at least 6 months, experienced disease progression whilst on tamoxifen (stratum 2); patients with recurrent metastatic disease during or within 12 months of discontinuing adjuvant tamoxifen (stratum 3). Of the 137 patients who received exemestane, 4 experienced a complete response (CR) and 28 a partial response (PR), for an overall response rate of 23%. Another 33 patients had SD for > or = 24 weeks, resulting in an overall success rate of 47%. The median time to objective response was 16.1 weeks (95% confidence interval (CI) 9.9-24.1). The median response duration was 69.4 weeks, the median duration of overall success 59.1 weeks, the median time to progression (TTP) 25.1 weeks and the median time to treatment failure (TTF) 24 weeks. Response to previous hormonal therapy had little effect on the results, except that there was a trend toward a higher overall success rate in patients who did not respond to previous hormonal therapy. After 8 weeks of therapy, serum levels of oestradiol (E2), oestrone (E1) and oestrone sulphate (E1S) were suppressed to 15.2%, 9.7% and 10.7% of baseline, respectively. The most common adverse events of drug-related or indeterminate cause were hot flushes (14%), dizziness (9%), nausea (8%) and increased sweating (5%). Exemestane had a favourable effect on performance status and tumour-related signs and symptoms, both of which improved or stabilised in approximately 67% and 68% of patients respectively. Exemestane is a unique therapy that is highly active and well tolerated as a new treatment for women with metastatic breast cancer.
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PMID:High activity and tolerability demonstrated for exemestane in postmenopausal women with metastatic breast cancer who had previously failed on tamoxifen treatment. 1088

Exemestane is an orally active steroidal aromatase inhibitor that has demonstrated efficacy in the treatment of postmenopausal patients with advanced breast cancer. This compound exhibits a good tolerability and safety profile, which may result from its highly selective mechanism of action. Exemestane binds irreversibly to the aromatase enzyme causing inactivation of the enzyme. This irreversible loss of enzyme may contribute to the sustained inhibition of estrogen synthesis noted following exemestane administration. Exemestane is a potent inhibitor of aromatization reducing estrogen synthesis in vivo by greater than 97%. The recommended dose of exemestane is 25 mg once daily. Although dosages up to 600 mg/day have been tested, the maximum tolerated dose of exemestane has not been reached in clinical study. The most frequently reported drug-related adverse events are hot flushes, nausea and fatigue, which are consistent with the estrogen-suppressive effects of the drug. Discontinuation due to adverse events is rare. Exemestane is a safe and well-tolerated alternative for the treatment of postmenopausal patients with advanced breast cancer.
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PMID:Exemestane in advanced breast cancer. 1108 51

Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.
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PMID:[Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer]. 1214 1

Aromatase inhibitors and inactivators are playing an increasing greater role in breast cancer treatment. Exemestane, a highly specific, steroidal aromatase inactivator, is the newest agent in this class. The drug is highly specific, and inhibits the in vivo conversion of androstenedione to oestrone (aromatization) by a mean of 97.9%. Exemestane has shown good efficacy and tolerability in multiple clinical trials among patients with metastatic breast cancer who have failed one or more previous hormonal therapies. Exemestane 25 mg/day slows disease progression and reduces tumour-related signs and symptoms and the drug exhibits a partial lack of cross-resistance with the non-steroidal aromatase inhibitors. Response rates to exemestane of 14% to 29% were observed including patients with visceral metastases, who have historically proven difficult to treat. In a large phase III trial, exemestane was found to be superior to megestrol acetate with respect to time to progression and overall survival. In addition, exemestane is currently under investigation as first-line therapy in metastatic disease and in sequence with tamoxifen in the adjuvant setting. Adverse events include low-grade hot flashes, nausea, and fatigue--mostly of mild to moderate intensity--and treatment-related discontinuations are rare. In conclusion, exemestane represents a novel and interesting drug for the treatment of advanced breast cancer, with exciting prospects for use in adjuvant therapy and, potentially, breast cancer prevention.
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PMID:Exemestane: a review of its clinical efficacy and safety. 1496 85