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| |  ECCO: Anastrozole As Effective As Tamoxifen For Advanced Breast Cancer In Postmenopausal Women VIENNA, AUSTRIA -- September 15, 1999 -- Early findings from a new study suggest that Tamoxifen, the current "gold standard" hormonal treatment for postmenopausal women with advanced breast cancer, could for the first time be seriously challenged by "Arimidex" (anastrozole) -- a new drug with a different mode of action. These findings, from a new North American study, were presented today at the ECCO conference in Vienna, Austria. The study is part of a large international two study programme involving over 1000 patients-both studies showed that anastrozole is at least as effective and well tolerated as tamoxifen, but the North American study also suggests that anastrozole is more effective. The data will be submitted to regulatory authorities with the aim of allowing doctors to prescribe anastrozole as a first-line treatment for advanced breast cancer in postmenopausal women. Anastrozole is currently widely used for the treatment of women whose disease has progressed following treatment with tamoxifen or other anti-estrogen. When approved, this will provide clinicians and postmenopausal patients with a choice of hormonal treatment options for advanced breast cancer. The findings from the North American study have taken experts in the field by surprise. Whilst the results showed that anastrozole is at least as effective as tamoxifen, they also showed that women in the study treated with tamoxifen had a 44 percent higher risk of their disease progressing than those treated with anastrozole. This suggests that anastrozole, which works in a different way to tamoxifen, could be a more effective treatment option for postmenopausal women with advanced disease-the first time that any non-tamoxifen like agent has challenged tamoxifen in this patient group. Prof. Jean-Marc Nabholtz, from the University of Alberta School of Medicine and the Cross Cancer Institute in Edmonton, Canada-one of the lead investigators from the North American study commented, "We know that tamoxifen and anastrozole are both effective treatments for postmenopausal women with advanced breast cancer, but until now, the two have never been compared directly in a clinical trial. What interested us is that the two drugs work in very different ways-tamoxifen primarily by blocking estrogen receptors in tumour cells, anastrozole by suppressing synthesis of estrogen, so that there is less to bind with estrogen receptors. Because they work differently, there are also possible differences between the two compounds in terms of their side-effect profiles." "Although these are early days, our results suggest that in this patient group, lowering estrogen levels with anastrozole is a very effective approach, as effective if not better than tamoxifen, and certainly merits further study. The two compounds appeared to be similar in terms of the number of side-effects reported, although differences were seen in the number of circulatory blood clots (thromboembolic events), which favoured the anastrozole treatment group. These results confirm the rationale for studying anastrozole in early stage operable breast cancer." The results of the other trial in the 1000 patient study programme, conducted in Europe, Latin America and Australasia, are also presented at ECCO this week and indicated that anastrozole is at least as effective as tamoxifen in this patient group. The reasons why the second study demonstrated that anastrozole is at least as effective as tamoxifen without demonstrating benefits for anastrozole over tamoxifen as the North American study did, have been the subject of much debate at the conference. Prof. Jacques Bonneterre from the Centre Oscar Lambret in Lille, France, and one of the lead investigators of this second study agrees with Prof. Nabholtz that they may have found the answer. "In our view, there is one obvious difference between the women studied in the two trials which may explain the results. Over 88 percent of the women in the North American study had breast cancer which was hormone-sensitive, while in our study, about 43 percent of the women were known to have hormone-sensitive tumours. If there is a real difference in the proportion of hormone-sensitive tumours between the two groups, this could be the reason why the North American group did so well." He continued, "We should not lose sight of the fact that this is the first time that an aromatase inhibitor has proven to be at least as effective as tamoxifen in these patients and the North American study certainly suggests that anastrozole could be significantly more effective. Anastrozole may even have some tolerability advantages. These findings alone mean that clinicians and patients have the prospect of an increased choice of therapies available to them." Long-term study: ATAC ("Arimidex", Tamoxifen Alone or in Combination) During the conference Professor Michael Baum, Professor of Surgery at University College Hospital, London, revealed that a long-term study comparing anastrozole with tamoxifen in early-stage operable breast cancer is already well underway and results are due in 2001. "ATAC will help us answer some vital questions about the comparative efficacy and safety of these two compounds, building on the early results presented by Prof. Nabholtz and Prof. Bonneterre this week," according to Professor Baum, Chairman of the ATAC steering committee. "As anastrozole and tamoxifen will also be given in combination in one arm of the study, ATAC will also allow us to investigate the intriguing possibility that giving the two treatments together could produce even better results for our patients." ATAC is the largest study of hormonal adjuvant treatment ever undertaken involving over 9,000 postmenopausal women from centres all over the world." It is a well established fact that altering the hormonal (endocrine) environment can be invaluable in patients with breast cancer. Both tamoxifen and anastrozole are used to alter the endocrine environment in order to produce a beneficial therapeutic effect in patients, but the two drugs work in different ways. Tamoxifen acts primarily as an anti-estrogen and blocks estrogen-receptors in cells. It disturbs normal cell response to estrogen by competing with the hormone for binding to the estrogen receptor in the tumour cell, thus inhibiting cellular proliferation. Because tamoxifen blocks estrogen receptors in tumour cells, a beneficial effect is seen in pre- and post-menopausal women with estrogen-positive (ER+) tumours i.e. "hormone sensitive" tumours, regardless of circulating estrogen levels in the blood. Anastrozole is a selective, non-steroidal aromatase inhibitor and differs from tamoxifen in the way it exerts a therapeutic effect by inhibiting a key step in the production of estrogen: anastrozole inhibits the conversion of androgens to estrogens by the enzyme aromatase. In this way, anastrozole suppresses the levels of estrogen circulating in the blood. Anastrozole is currently available in most countries for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following treatment with tamoxifen or other antiestrogens. In this indication, anastrozole has been shown to be highly effective with a significant survival advantage over megestrol actetate, and to be well tolerated when administered over prolonged periods. The most common side-effects of anastrozole treatment being hot flushes and gastrointestinal disturbances. Anastrozole is currently approved for the first-line treatment of advanced breast cancer in postmenopausal women in Finland, S. Africa and Ireland. This new data will be submitted to regulatory authorities in the near future in order to obtain a broader approved indication for the use of anastrozole in advanced breast cancer in postmenopausal women. The two anastrozole/tamoxifen trials presented at ECCO were randomised, double-blind, double-dummy studies designed to demonstrate equivalent efficacy of the two treatments in postmenopausal women with advanced breast cancer eligible for hormone therapy (confirmed hormone-sensitive or status unknown). The women were either newly diagnosed with advanced disease or had progressed following diagnosis and treatment of early disease. Patients were randomised on a 1:1 basis to receive either 1mg anastrozole or 20mg tamoxifen daily. The primary endpoints of the studies were time to progression, objective response and tolerability.
Related Links: Tamoxifen and Arimidex.
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