ARIMIDEX™: A new oral, once-a-day aromatase inhibitor

Plourde, Paul V.; Dyroff, Martin C.; Dowsett, Mitch; Demers, Laurence M.; Yates, Roger; Webster, Alan

doi:10.1016/0960-0760(95)00045-2

Cited by 118 publications

(66 citation statements)

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“…If post-treatment levels were elevated, they were repeated 4 weeks after treatment was completed. The assay used extraction and radioimmunoassay plus chromatography to detect changes in plasma estradiol of 1-5 pg/mL [21][22][23][24]. The analyst was blind to the identity of the patient and to whether samples were obtained before or after treatment.…”

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confidence: 99%

Topical Testosterone for Breast Cancer Patients with Vaginal Atrophy Related to Aromatase Inhibitors: A Phase I/II Study

et al. 2011

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After completing this course, the reader will be able to:1. Evaluate early data regarding the impact of daily vaginal testosterone on estradiol and testosterone levels in breast cancer patients receiving treatment with aromatase inhibitors.2. Explain the potential clinical benefits of vaginal testosterone therapy to treat vaginal atrophy in women with breast cancer receiving long-term aromatase inhibitor therapy.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME The Oncologist CME Program is located online at http://cme.theoncologist.com/. To take the CME activity related to this article, you must be a registered user. ABSTRACT Breast CancerThe

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Section: Measurementsmentioning

confidence: 99%

Topical Testosterone for Breast Cancer Patients with Vaginal Atrophy Related to Aromatase Inhibitors: A Phase I/II Study

et al. 2011

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“…Pilot studies in post-menopausal women have shown the drug to suppress plasma E2 by > 80% (Plourde et al, 1994), and preclinical studies as well as observations in women suggest the drug to be highly specific with no influence on adrenal steroid synthesis (Plourde et al, 1995). A major problem in evaluating the biochemical efficacy of aromatase inhibitors has been the lack of internal consistency between the percentage aromatase inhibition and degree of plasma oestrogen suppression.…”

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confidence: 99%

“…We have developed a high-performance liquid chromatography (HPLC) technique to improve the specificity and sensitivity of measuring the isotope ratio in urinary oestrogen metabolites . A recent formal assessment of sensitivity indicated that inhibition of up to 99.1% was detectable (Dowsett et al, 1995). In the present study, each patient had in vivo aromatisation determined before commencing treatment and at the end of period I and II by use of this urinary HPLC technique.…”

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Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer

Geisler

King²,

Dowsett³

et al. 1996

Br J Cancer

328

149

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Sununary The effect of anastrozole ('Arimidex', ZD1033), a new, selective, non-steroidal aromatase inhibitor on in vivo aromatisation and plasma oestrogen levels was evaluated in post-menopausal women with breast cancer. Twelve patients progressing after treatment with tamoxifen were randomised to receive anastrozole 1 mg or 10 mg once daily for a 28 day period in a double-blinded crossover design. In vivo aromatisation and plasma oestrogen levels were determined before commencing treatment and at the end of each 4-week period. Breast cancer is the most common malignancy among women in the western hemisphere. Many of these patients develop metastatic disease, for which no cure is currently available. Because endocrine treatment causes fewer side-effects than chemotherapy, such therapy is first-line treatment in patients with metastatic disease and hormone receptor-positive tumours. While the anti-oestrogen tamoxifen is first choice of therapy in post-menopausal patients with metastatic breast cancer. increasing use of tamoxifen as adjuvant therapy focuses on the need for alternative endocrine treatment options on relapse in breast cancer patients.While ovarian oestrogen synthesis ceases at the menopause, oestrogens are synthesised in peripheral tissue from circulating androgens by the process called aromatisation (Grodin et al., 1973). The main pathway is conversion of androstenedione (A) into oestrone (El), with a minor contribution from conversion of testosterone into oestradiol (E2) (L0nning et al., 1990).Aromatase inhibitors are drugs that inhibit the peripheral conversion of androgens to oestrogens (Santen et al., 1982a), thereby suppressing plasma oestrogen levels in postmenopausal women. The first-generation aromatase inhibitor, aminoglutethimide, was implemented in breast cancer treatment more than 20 years ago (Cash et al., 1967). While the drug is effective in hormone-sensitive breast cancer, lack of specificity (inhibition of adrenal steroid-synthesising enzymes) and side-effects (such as skin rash and lethargy) provoked the development of new aromatase inhibitors (Coombes et al., 1984;Evans et al., 1992;Johnston et al., 1994;Lipton et al., 1995; Santen et al., 1989).Anastrozole (Arimidex; 2,2'[5-(1H-1 ,2,4-triazol-1-ylmethyl) -1,3-phenylene]bis-(2-methylpropiononitrile, Figure 1) is a new, potent and selective aromatase inhibitor belonging to the triazole class. Pilot studies in post-menopausal women have shown the drug to suppress plasma E2 by > 80% (Plourde et al., 1994), and preclinical studies as well as observations in women suggest the drug to be highly specific with no influence on adrenal steroid synthesis (Plourde et al., 1995). A major problem in evaluating the biochemical efficacy of aromatase inhibitors has been the lack of internal consistency between the percentage aromatase inhibition and degree of plasma oestrogen suppression. While aminoglutethimide as well as the second-generation aromatase inhibitor formestane and the third-generation inhibitor fadrozole (L0nning et al., 1991) ...

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“…Anastrozole is a potent, orally active, selective, non-steroidal AI that markedly reduces the levels of circulating oestrogens in postmenopausal women with breast cancer (Plourde et al, 1995;Geisler et al, 1996). As a second-line agent for adjuvant therapy in postmenopausal women with advanced breast cancer, anastrozole has been shown to offer significant clinical benefits when compared with the progestin, megestrol acetate (MA) (Buzdar et al, 1996(Buzdar et al, , 1998.…”

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Anastrozole (‘Arimidex’) blocks oestrogen synthesis both peripherally and within the breast in postmenopausal women with large operable breast cancer

et al. 2002

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The effect of anastrozole on peripheral and tumour aromatase activity and oestrogen levels in postmenopausal patients with oestrogen receptor-rich breast tumours was investigated. Twenty-six patients were randomly allocated to treatment with anastrozole 1 mg (n=13) or 10 mg (n=13), once daily. Before and after 12 weeks' treatment, patients were infused with 3 H-D 4 androstenedione (20 MBq) and 14 C-oestrone (E 1 ) (1 MBq) for 18 h. Oestrogens were purified from excised tumours and plasma samples taken after each infusion. Peripheral and tumour aromatase activity and tumour E 1 uptake were calculated from levels of 3 H and 14 C in purified E 1 fractions from tumour and plasma. Endogenous tumour oestrogens were measured by radioimmunoassay. Twenty-three patients were available for analysis (1 mg group, n=12; 10 mg group, n=11). Following treatment, anastrozole (1 and 10 mg) markedly inhibited peripheral aromatase in all patients (the difference between pre-and on-treatment values being highly significant P50.0001). In situ aromatase activity was also profoundly decreased by anastrozole treatment in 16 of 19 tumours (the difference with treatment also being highly significant P=0.0009). Most tumours were able to concentrate E 1 beyond levels in the circulation; anastrozole treatment had no consistent effect on uptake of E 1 . Endogenous tumour levels of both E 1 and oestradiol (E 2 ) were significantly reduced with therapy (P=0.028 for E 1 and P=0.0019 for E 2 ). Anastrozole (1 and 10 mg daily) effectively suppresses aromatase activity, and subsequently oestrogen levels, within the breast tissue of postmenopausal women with large or locally advanced, operable, oestrogen receptor-rich breast cancers.

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ARIMIDEX™: A new oral, once-a-day aromatase inhibitor

Cited by 118 publications

References 5 publications

Topical Testosterone for Breast Cancer Patients with Vaginal Atrophy Related to Aromatase Inhibitors: A Phase I/II Study

Topical Testosterone for Breast Cancer Patients with Vaginal Atrophy Related to Aromatase Inhibitors: A Phase I/II Study

Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer

Anastrozole (‘Arimidex’) blocks oestrogen synthesis both peripherally and within the breast in postmenopausal women with large operable breast cancer

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