Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Since the introduction of the first generation aromatase inhibitor, aminoglutethimide, for breast cancer treatment 30 years ago, we now have at hand novel, potent and well-tolerated steroidal and non-steroidal compounds, allowing near complete inhibition of oestrogen synthesis. The third-generation aromatase inhibitor, or more accurately termed inactivator, exemestane, is a potent suppressor of oestrogen synthesis and is shown to be an effective antitumour agent in postmenopausal breast cancer patients. Exemestane has been shown to be effective in patients failing multiple endocrine regimens. A large randomised study has revealed that exemestane improves time-to-disease progression as well as overall survival compared with megestrol acetate as second-line therapy in patients failing tamoxifen. In current studies, exemestane is compared with tamoxifen as first-line therapy for metastatic disease. Sequential therapy with tamoxifen followed by exemestane is also being compared with tamoxifen monotherapy in the adjuvant setting. In addition, the drug may have potential for breast cancer prevention.
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PMID:Pharmacology and clinical experience with exemestane. 1106 Jul 85

Anti-aromatase agents now have a central role in the management of breast cancer in postmenopausal women; they are superior to megestrol acetate as second-line therapy and to tamoxifen for initial therapy of metastatic disease. They also are highly active as neoadjuvant therapy. Two classes of anti-aromatase agents are available: steroidal (eg, exemestane) and nonsteroidal (eg, anastrozole, letrozole). Although both types of agents act on the aromatase enzyme, they do so by different mechanisms and have different effects on cellular aromatase activity. Nonsteroidal agents are associated with increased aromatase enzyme content and steroidal agents are associated with decreased content. The increase in aromatase content seen with the nonsteroidal agents may in part explain the development of resistance with these agents and the ability of the steroidal agent exemestane to induce a response when nonsteroidal agents fail. Because the anti-aromatase agents almost completely eliminate endogenous estrogen production, they not only affect breast cancer tissues, but also may alter the function of other estrogen-responsive tissues. However, preclinical data show that the steroidal agent exemestane may actually improve bone and lipid metabolism. In addition, no increase in clinical fracture rate has been noted in women treated with exemestane in metastatic trials; the fracture risk has not yet been studied following prolonged exposure in healthy women. Exemestane associated beneficial effects on these end organs may be due to the steroidal nature of both the parent compound and its principal metabolite, 17-hydroexemestane. Similar benefits have not been reported with nonsteroidal antiaromatase agents. Based on their excellent activity in the metastatic setting, anti-aromatase agents are now being evaluated in the adjuvant setting and in pilot studies for chemoprevention. These studies will provide long-term data in healthy women and will help to differentiate anti-aromatase agents, in terms of their efficacy in the treatment of breast cancer and their effects on end organs.
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PMID:Anti-aromatase agents in the treatment and prevention of breast cancer. 1196 25

Exemestane is a novel, potent, and specific third-generation aromatase inactivator developed for breast can-cer therapy. The drug is effective in patients with metastatic disease failing tamoxifen alone or tamoxifen followed by megestrol acetate or a nonsteroidal aromatase inhibitor. In a phase III study, exemestane was superior to megestrol acetate in overall survival, time to tumor progression, and time to treatment failure in women with metastatic disease who experienced failure of tamoxifen. Preliminary evidence suggests activity to exemestane exceeds that obtained with tamoxifen as first-line treatment. Two studies are comparing sequential treatment with tamoxifen followed by exemestane to tamoxifen monotherapy in the adjuvant setting. A third study is comparing the toxicity profile of exemestane with that of placebo in patients with early breast cancer who are at low risk of relapse. The findings from these studies will determine the role of exemestane in early breast cancer and lay the foundation for assessing its potential role in breast cancer prevention.
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PMID:Exemestane in breast cancer: current status and future directions. 1197 Jul 47

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

A 76-year-old woman was diagnosed with advanced breast cancer with bilateral multiple lung and pleural metastases in March 2003. Her CEA and CA15-3 level were 7.6 ng/ml and 98.3 U/l, respectively. However, she refused intensive chemotherapy and chose a hormonal monotherapy with exemestane instead. The patient then did not return to our department for about one year, during which time she continued to take the same medications. When she visited again, CEA and CA15-3 level were reduced to within the normal range, and her multiple lung and pleural metastases were found to have almost completely disappeared upon computed tomography. Exemestane is expected to be an effective agent for the treatment of hormonal receptor-positive postmenopausal woman with life-threatening advanced breast cancer.
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PMID:[A case of aged advanced breast cancer with multiple lung and pleural metastases responding to exemestane monotherapy]. 1550 49

Rapid advances in the treatment of breast cancer, especially in the form of hormone therapy have truly increased the hope of longer and better disease-free survival for these patients. Exemestane, a third generation aromatase inhibitor has been extensively evaluated in metastatic as well as adjuvant therapy of breast cancer. It has also been evaluated for its safety profile, especially on bone and lipids. Exemestane provides hope to the patients with breast cancer both in early and metastatic disease. This review analyzes all the aspects of exemestane therapy.
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PMID:Exemestane: a milestone against breast cancer. 1749 83

A 60-year-old woman with Stage II, ER-positive, PgR-positive, HER2 (2+) cancer in the right breast underwent right mastectomy with right axillary dissection after chemotherapy with EC followed by docetaxel (DOC) alone. Exemestane was used for postoperative adjuvant treatment. She underwent a right chest wall tumor resection for local recurrence. Hormone therapy was continued with toremifene in place of exemestane. In December 2007, two years after the second surgery, CEA was elevated and PET showed a local recurrence in the right chest wall and metastases to the right axillary nodes and liver. The tumor was ER-positive, PgR-negative and HER2 (3+) at recurrence, and vinorelbine/trastuzumab combination was initiated as first-line chemotherapy for the recurrent lesion and liver metastasis. All lesions in the right chest wall, right axillary nodes and liver disappeared from PET and CT images after five courses of the regimen, resulting in clinical CR. Vinorelbine combined with trastuzumab appears to be a useful therapy for HER2-positive recurrent breast cancer.
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PMID:[A case of recurrent breast cancer responding to vinorelbine/trastuzumab combination therapy]. 2000 69

To undertake a systematic review of three first-line treatments (letrozole, anastrozole and exemestane) for hormone sensitive advanced or metastatic breast cancer (MBC) in post-menopausal women. We searched six databases from inception up to January 2009 for relevant trials regardless of language or publication status. Randomised controlled clinical trials assessing the safety and efficacy of first-line AIs for post-menopausal women with hormone receptor-positive (HR+, i.e. ER+ and/or PgR+) with or without ErbB2 (HER2)-positive MBC, who have not received prior therapy for advanced or metastatic disease were included. Where meta-analysis using direct or indirect comparisons was considered unsuitable for some or all of the data, we employed a narrative synthesis method. Four studies (25 papers) met the inclusion criteria. From the available evidence, it was possible to directly compare the three AIs with tamoxifen. In addition, by using a network meta-analysis it was possible to compare the three AIs with each other. Based on direct evidence, letrozole seemed to be significantly better than tamoxifen in terms of time-to-progression (TTP) (HR = 0.70 (95% CI: 0.60, 0.82)), objective response rate (RR = 0.65 (95% CI: 0.52, 0.82)) and quality-adjusted time without symptoms or toxicity (Q-Twist difference = 1.5; P < 0.001). Exemestane seemed significantly superior to tamoxifen in terms of objective response rate (RR = 0.68 (95% CI: 0.53, 0.89)). Anastrozole seemed significantly superior to tamoxifen in terms of TTP in one trial (HR = 1.42 (95% CI: 1.15, NR)), but not in the other (HR = 1.01 (95% CI: 0.87, NR)). In terms of adverse events, no significant differences were found between letrozole and tamoxifen. Tamoxifen was associated with significantly more serious adverse events in comparison with exemestane (OR = 0.61 (95% CI: 0.38, 0.97)); while exemestane was associated with significantly more arthralgia in comparison with tamoxifen (OR = 2.33 (95% CI: 1.07, 5.11)). Anastrozole was associated with significantly more total adverse events (OR = 1.04 (95% CI: 1.00, 1.09)) and hot flushes (OR = 1.39 (95% CI: 1.03, 1.89)) in comparison with tamoxifen in one trial; however, the other trial showed no significant differences in adverse events between anastrozole and tamoxifen. The indirect comparison of AIs with each other in women with post-menopausal, hormone sensitive advanced or MBC showed that letrozole and exemestane were better in terms of objective response rate than anastrozole; while the more clinically relevant outcomes overall survival (OS) and progression-free survival (PFS) showed no significant differences between AIs. OS and PFS showed no significant differences between AIs and hence based on these results a class effect for all AIs is possible. However, these results are based on indirect comparisons and a network analysis for which the basic assumptions of homogeneity, similarity and consistency were not fulfilled. Therefore, despite the fact that these are the best available data, the results need to be interpreted with appropriate caution. Head-to-head comparisons between letrozole, anastrozole and exemestane in the first-line MBC setting are warranted.
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PMID:Systematic review of aromatase inhibitors in the first-line treatment for hormone sensitive advanced or metastatic breast cancer. 2053 42

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.
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PMID:Endocrine therapy for postmenopausal women with hormone receptor-positive her2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement. 2344 28


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