Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on aminoglutethimide: a phase ii multicentre multinational study

Thürlimann, Beat; Paridaens, Robert; Serin, D.; Bonneterre, Jacques; Roché, Henri; Murray, Robin M.; Salle, E. Di; Lanzalone, Silvana; Zurlo, Marco; Piscitelli, G.

doi:10.1016/s0959-8049(97)00283-9

Cited by 131 publications

(38 citation statements)

References 16 publications

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“…Upon progression of metastatic disease following treatment with NSAIs, exemestane may be effective as sequential hormone therapy (Lønning et al 2000, Bertelli & Paridaens 2006, Steele et al 2006, Lønning 2009, Kim et al 2012. Several trials have found that breast cancer patients who have become resistant to NSAIs may experience benefit from SAIs (Table 2; Thürlimann et al 1997, Lønning et al 2000, Bertelli et al 2005, Iaffaioli et al 2005, Gennatas et al 2006, Mayordomo et al 2006, Steele et al 2006, Carlini et al 2007, Chin et al 2007, Mauriac et al 2009). On average, 25-30% of patients in these cross-over studies experienced objective response or stable disease for 6 months or more.…”

Section: In the Evaluation Of Faslodex Vs Exemestane Clinicalmentioning

confidence: 99%

“…It has been found that changing from one AI-class to another, regardless of the sequence, can result in 0-26% ORR and that 50-62% of these patients achieve stable disease (Thürlimann et al 1997, Zilembo et al 2004, Bertelli et al 2005, Chia et al 2008, Miller et al 2008. The exact mechanism of nontotal cross-resistance however is not yet known.…”

Section: Perspectivesmentioning

confidence: 99%

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Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Asten¹,

Neven²,

Lintermans³

et al. 2014

Endocrine-Related Cancer

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Breast cancer is the most prevalent type of cancer in women and responsible for significant female cancer-related mortality worldwide. In the Western world, over 80% of breast cancers are hormone-receptor positive for which endocrine therapy is administered. The main anti-estrogen treatments in use consist of selective estrogen-receptor modulators, such as tamoxifen, and third-generation aromatase inhibitors (AIs), such as exemestane, letrozole, and anastrozole. In this review, the focus will lie on exemestane, its clinical use, and its side-effect profile. Exemestane is the only third-generation steroidal AI. Its efficacy as a first-line treatment in metastatic breast cancer has been demonstrated. Therefore, exemestane could be considered a valid first-line therapeutic option, but it also can be used in second-line or further situations. Exemestane is mostly used as part of sequential adjuvant treatment following tamoxifen, but in this setting it is also active in monotherapy. Furthermore, this AI has been studied in the neoadjuvant setting as presurgical treatment, and even as chemoprevention in high-risk healthy postmenopausal women. It may reverse side effects of tamoxifen, such as endometrial changes and thromboembolic disease but may also cause some inconvenient side effects itself. Additionally, there is a lack of total crossresistance between exemestane and nonsteroidal AIs as far as their anti-tumoral efficacy is concerned; moreover the two classes of AIs display a nontotal overlapping toxicity profile. Taking together, exemestane can be considered as a useful treatment option at all stages of breast cancer.

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Section: In the Evaluation Of Faslodex Vs Exemestane Clinicalmentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Asten¹,

Neven²,

Lintermans³

et al. 2014

Endocrine-Related Cancer

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“…This effect is observed regardless of the treatment sequence: nonsteroidal AI followed by steroidal AI [48 -56] or steroidal AI followed by nonsteroidal AI [55,57]. It must be noted that these were open-label trials, many of which were single-center studies with a small number of enrolled patients, receiving a range of prior and/or concomitant therapies (e.g., chemotherapy), and at least one study used a higher dose of the second AI than is recommended [51].…”

Section: Clinical Implications Crossresistance and Sequential Therapymentioning

confidence: 99%

Aromatase Inhibitors: Are There Differences Between Steroidal and Nonsteroidal Aromatase Inhibitors and Do They Matter?

et al. 2008

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Disclosure: W.R.M. discloses that this article discusses letrozole (Novartis), anastrozole (AstraZeneca), and exemestane (Pfizer) for validation of mechanism of action. He has also been on the advisory board for Pfizer and received speaker's honoraria. J.B. has received honoraria and research funding from Pfizer (exemestane). A.M.H.B. has received honoraria and research support from AstraZeneca (anastrozole research). R.W.B. discloses that this article discusses exemestane (Pfizer), anastrozole (AstraZeneca), and letrozole (Novartis) for use in breast cancer therapy. He also received an honorarium for participating in an expert panel meeting from Pfizer/CC Ford Healthcare. E.d.S. is an employee and has stock options in Pfizer (exemestane). P.E.L. has received speaker's honoraria from Novartis, AstraZeneca, and Pfizer. A.L. discloses no conflict of interest. N.M. discloses that the article discusses exemestane (Pfizer), anastrozole (AstraZeneca), and letrozole (Novartis) for breast cancer treatment, and he has been on an advisory board and received honoraria from Pfizer (exemestane). T.M. has research funding from Novartis (letrozole) and has received a consulting fee from Pfizer (exemestane). H.S. has research funding and has received an honorarium from Pfizer (exemestane). P.E.G. discloses that this article discusses letrozole (Novartis), anastrozole (AstraZeneca), and exemestane (Pfizer) for validation of mechanism of action. He also discloses that the article discusses aromatase inhibitors for prevention (Novartis, AstraZeneca, Pfizer), and that he has received speaker's honoraria from Novartis, AstraZeneca, and Pfizer. The content of this manuscript has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from any commercial bias; they have disclosed no financial relationships relevant to this content.

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“…Notably, that study (Lønning et al 2000) revealed little difference in response rates between patients who had previously failed on a third generation non-steroidal compound versus those who had failed on aminoglutethimide (20 versus 27%). While the findings in some studies that patients failing aminoglutethimide responded to exemestane (Thu¨rlimann et al 1997b, Lønning et al 2000 could be explained by a more potent aromatase inhibition with the second compound, the findings that patients may respond I II III IV IV V VI AG, aminoglutethimide; Ana, anastrozole; Exe, exemestane; For, formestane; nAI, non-steroidal third generation aromatase inhibitors (anastrozole, letrozole and vorozole); RR, response rate; S.D., ! 6 months (mo).…”

Section: Lack Of Cross-resistance To Aromatase Inhibitors and Inactivmentioning

confidence: 99%

Aromatase inhibitors in breast cancer.

Lønning¹

2004

Endocr Relat Cancer

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The development of aromatase inhibitors for breast cancer therapy is a result of successful translational research exploring the biochemical effects of different compounds in vivo. Studies assessing plasma oestrogen levels as well as in vivo aromatase inhibition have revealed a consistent difference with respect to biochemical efficacy between the third generation compounds (anastrozole, letrozole and exemestane) and the previous, first and second generation drugs, corresponding to the improved clinical effects of these compounds as outlined in large phase III studies. Thus, endocrine evaluation has been found to be a valid surrogate parameter for clinical efficacy. Moreover, the results from these studies have added important biological information to our understanding of endocrine regulation of breast cancer. Based on the clinical results so far, aromatase inhibitors are believed to play a key role in future adjuvant therapy of postmenopausal breast cancer patients and potentially also for breast cancer prevention. Interesting findings such as the lack of cross-resistance between steroidal and non-steroidal compounds should be further explored, as this may add additional information to our understanding of breast cancer biology.

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Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on aminoglutethimide: a phase ii multicentre multinational study

Cited by 131 publications

References 16 publications

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Aromatase Inhibitors: Are There Differences Between Steroidal and Nonsteroidal Aromatase Inhibitors and Do They Matter?

Aromatase inhibitors in breast cancer.

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