Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighty previously treated postmenopausal women with metastatic breast cancer were randomized to receive fadrozole (CGS 16 949A), a new aromatase inhibitor, 1 or 4 mg orally per day. Seventy eight patients were evaluable for toxicity and response. Only mild to moderate toxicity, namely hot flushes (28%), nausea and vomiting (13%), fatigue (8%) and loss of appetite (5%) occurred. Complete response was documented in 10% and partial response in 13% of patients with 45% having a no change status for at least 2 months. The median time to treatment failure is 4.1 months. The median survival is 23.7 months. The median survival is 23.7 months. The response and survival in patients with estrogen receptor positive and estrogen receptor unknown disease were not significantly different. Neither response nor survival was significantly different between the patients receiving 1 or 4 mg of fadrozole per day. Fadrozole is a well tolerated, effective second line treatment for women with metastatic breast cancer.
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PMID:Fadrozole hydrochloride, a new nontoxic aromatase inhibitor for the treatment of patients with metastatic breast cancer. 138 48

4-hydroxyandrostenedione, a potent inhibitor of the aromatase (oestrogen synthetase) system, was given to 11 patients with metastatic breast cancer. After a single 500 mg intramuscular injection a sustained reduction of serum oestradiol was observed for at least 1 week in all patients in whom the steroid was measured. 4 patients responded to treatment for periods of up to 4 months, and healing of bone metastases and reduction in size of soft-tissue metastases was evident. The only side-effects were pain at the injection site and hot flushes. 4-hydroxyandrostenedione is a new and specific aromatase inhibitor which shows promise in the treatment of patients with metastatic breast cancer.
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PMID:4-Hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. 615 Feb 77

Vorozole is a triazole derivative which binds to the cytochrome P450 moiety of aromatase, thus causing reversible inhibition of the enzyme. Plasma estradiol levels are reduced by about 90% in postmenopausal women treated with vorozole. Phase II clinical studies found vorozole to be an effective agent for the treatment of postmenopausal women with advanced breast cancer, achieving objective responses in up to 35% of patients. In 2 large phase III studies, vorozole 2.5 mg/day demonstrated favourable clinical efficacy compared with aminoglutethimide and megestrol. Vorozole improved patients' quality of life to a greater extent than aminoglutethimide. Clinical trials to date indicate that the tolerability of vorozole is better than that of aminoglutethimide. Vorozole also appears to be at least as well tolerated as megestrol (although inappropriate bodyweight gain is more common in megestrol recipients). The most common adverse events with vorozole are hot flushes, and nausea, which are generally mild in severity.
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PMID:Vorozole. 930 82

The aim of the study was to compare efficacy and tolerability of the new aromatase inhibitor formestane (Lentaron) with megestrol acetate (Megestat) (MGA) in postmenopausal patients with advanced breast cancer. 179 patients were randomised to receive either 250 mg formestane intramuscularly biweekly or MGA 160 mg orally daily. 51% of the patients had received tamoxifen as adjuvant treatment; 73% of the patients had positive and 16% unknown oestrogen receptor values. The response rate was 17% in both treatment arms (95% confidence interval 10-26% for formestane and 10-27% for MGA). Disease stabilisation > or = 6 months was seen in 25% of the formestane and 22% of the MGA patients. Time to treatment failure was 120 days in the formestane arm and 111 days in the MGA arm. There was no significant difference between the treatments with regard to response rate and time to treatment failure. Overall toxicity was similar in both arms, but weight gain > 3 kg (P = 0.081) and severe cardiovascular toxicity (P = 0.044) were more frequently observed with MGA, e.g. deep vein thrombosis 0/90 formestane versus 5/81 MGA cases (P = 0.022). Formestane was associated with worsening of hot flushes/sleeping problems (P = 0.051) and mild leucopenia (P = 0.004). In our study, formestane and MGA showed similar antineoplastic activity as second-line hormonal treatment for advanced breast cancer. Both drugs have a specific toxicity profile. MGA was associated with significantly more severe cardiovascular toxicity and weight increase than formestane.
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PMID:Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Swiss Group for Clinical Cancer Research (SAKK) 937 2

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

Vorozole (Rivizor) is a potent and stereospecific inhibitor of aromatase having shown promising endocrine effects in phase I studies. In the present trial, 27 postmenopausal patients with advanced breast cancer, measurable lesions, presumably hormone responsive (ER or PR+, or ER? with disease-free survival longer than 1 year, or prior documented response to tamoxifen), were treated with vorozole one tablet 2.5 mg daily. All had been previously treated with tamoxifen as adjuvant (two patients) or for advanced disease (24 patients), or both (one patient). Objective remissions were observed in eight patients (30%) with two complete responses (CR) and six partial responses (PR) lasting for a median of 14.3 months (range 6.8-40.6); nine stabilizations were also recorded (median 7.9 months; range 3.7-40.1). Median time to progression for the 27 patients was 5.9 months. Sites of response were skin (three patients), lymph nodes (two patients), lung (two patients) and chest wall plus lymph nodes (one patient). Treatment was very well tolerated: mild hot flushes (four patients), gastrointestinal complaints (four patients) and no significant toxicity (common toxicity criteria grade above 2) or drug-related severe adverse event. It is concluded that vorozole is an active second-line endocrine treatment, deserving consideration for randomized comparison with other agents such as aminoglutethimide, megestrol acetate or medroxyprogesterone acetate.
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PMID:Vorozole (Rivizor): an active and well tolerated new aromatase inhibitor for the treatment of advanced breast cancer patients with prior tamoxifen exposure. Investigational Drug Branch of the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer Cooperative Group. 949 89

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

Third-generation aromatase inhibitors are able to reduce circulating plasma estrogen concentrations in postmenopausal women to below detectable limits and significantly inhibit aromatase, the enzyme responsible for estrogen synthesis, in normal breast tissue and breast tumors. Their role in the treatment of advanced breast cancer is well established and their use in adjuvant therapy is currently being explored. On the basis of these trials, evaluation of these inhibitors in the prevention of breast cancer may be appropriate. Aromatase inhibitors have non-specific toxic side effects including (but not limited to): asthenia, headache, nausea, peripheral edema, fatigue, vomiting and dyspepsia. In addition, certain endocrinological side effects in postmenopausal women are notable, namely hot flushes and vaginal dryness. In advanced breast cancer, these side effects result in treatment withdrawal in few (<4%) women. Of concern, however, are the potential long-term endocrinological side effects in women receiving treatment as first-line adjuvant therapy or in sequence or combination with tamoxifen or other selective estrogen receptor modulators (SERMs). Current studies of adjuvant treatments for breast cancer in healthy women are carefully evaluating, in addition to general toxicities, the effects on bone, lipid metabolism, cardiovascular risk, quality of life and menopausal symptoms. Careful evaluation of all-cause morbidity and mortality is necessary to plan trials and justify long-term use of aromatase inhibitors in the treatment or prevention of breast cancer in healthy women.
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PMID:Risks versus benefits in the clinical application of aromatase inhibitors. 1073 Nov 26

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


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