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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Given orally, anastrozole is used for the adjuvant treatment of ER+ve invasive breast cancer in postmenopausal women with a recommended duration of treatment of 2–3 years. It is useful for treating postmenopausal women who are unable to take tamoxifen because of a high risk of thromboembolism or endometrial abnormalities. In the UK, NICE recommends anastrozole for the adjuvant treatment of ER+ve early and/or invasive breast cancer in postmenopausal women with or without previous (i.e., 2–3 years) tamoxifen therapy. It is also recommended for the chemoprevention of breast cancer, but it is not licensed for this indication.
Breast Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Amy Case, Gwenllian Edwards, Catherine Pembroke
A series of adjuvant trials with AIs including over 30,000 women have been completed and have established the place of AIs in the management of postmenopausal women with breast cancer. AIs have been explored (1) as replacement for tamoxifen,100 (2) following 2–3 years of tamoxifen,101 (3) following 5 years of tamoxifen,102 and (4) as an extended therapy over 10 years. Updated results from the Arimidex or Tamoxifen Alone or in Combination (ATAC) trial,103 Breast International Group (BIG) 1-98 Femara-Tamoxifen trial,104 and Intergroup Exemestane Study105 all showed a small but statistically significant improvement in relapse-free survival (and in some cases OS) for the AIs over tamoxifen when administered in the first 5 years. The MA17 trial (testing letrozole 2.5 mg daily after 5 years of tamoxifen) also reported a significantly superior DFS in favor of letrozole (and a significant OS benefit), with the consequence that this option has become standard of care for high-risk patients who have completed 5 years of adjuvant tamoxifen therapy.102 To date, there is limited evidence of the value of extending AI therapy to 10 years. Although extended treatment reduces the rate of disease recurrence and contra-lateral breast cancer, the absolute effect is modest, and the MA.17R trial found no difference in overall survival with the additional treatment.106 In terms of choice of agent, a recent study has reported equivalent efficacy between anastrozole and letrozole.107
Chemoprevention and endocrine therapy of endometrial carcinoma
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
The new non-steroidal aromatase inhibitors anastrozole and letrozole have been recently assessed for breast cancer treatment3,66,67. Letrozole has been shown to be significantly superior to megestrol acetate in overall response rates and time to treatment failures, whereas anastrozole has been found to improve survival in comparison with megestrol acetate66. Moreover, anastrozole showed a significant advantage over tamoxifen in terms of time to progression as first-line therapy for advanced breast cancer in postmenopausal women67. As for endometrial cancer, Rose and colleagues65 achieved an objective response in 9% of 23 patients with advanced or recurrent disease who had received no more than one prior hormone therapy regimen. Median progression-free survival and overall survival were 1 and 6 months, respectively. The National Cancer Institute of Canada is currently carrying out a phase II study on letrozole in women with recurrent or metastatic adenocarcinoma or adenosquamous carcinoma of the endometrium not curable by surgery or radiotherapy68.
Aromatase inhibitors in the pharmacotherapy of endometriosis
Published in Expert Opinion on Pharmacotherapy, 2023
Barbara Gardella, Edoardo Rispoli, Marianna Francesca Pasquali, Matteo Mauri, Valentina Musacchi, Mattia Dominoni
Alternative routes of administration of AIs are being investigated. There is only one study by Hefler et al. on the use of anastrozole in a vaginal suppository form. It was an open-label trial in which 10 premenopausal patients were treated with 0,25 mg anastrozole daily for 6 months having benefits only for dysmenorrhea and quality of life. Mixed results on lesion dimensions meaning that in three patients the lesions decreased in size, in three patients they remained stable, and in three patients they increased. No effects were observed on bone mineral density. The dosage of anastrozole was extrapolated from pharmacokinetic data on danazol suppositories and the expected absorption capacity of the vaginal wall. Vaginal rings containing a combination of anastrozole and levonorgestrel are being investigated. While it is established that 40 mcg/day of levonorgestrel is enough to cause an ovarian suppression comparable to systemic treatment, the dose of anastrozole is still under investigation in this trial (NCT02203331), so data is still lacking on this topic.
Benefit–risk profile of black cohosh (isopropanolic Cimicifuga racemosa extract) with and without St John’s wort in breast cancer patients
Published in Climacteric, 2019
X. Ruan, A. O. Mueck, A.-M. Beer, B. Naser, S. Pickartz
Anastrozole metabolites (triazole, hydroxyanastrozole, hydroxyanastrozole glucuronide, and anastrozole glucuronide) result from N-dealkylation, hydroxylation, and glucuronidation processes (Figure 2)95,96. The main metabolite, triazole, is inactive95. Enzymes involved in anastrozole metabolism have not been completely identified95. In vitro, the formation of hydroxyanastrozole was mainly catalyzed by CYP3A4/5 and, to a lesser extent, by CYP2C8, CYP2D6, and CYP2B6 (Figure 2)95,97. CYP3A4 inducers could possibly increase the production of one of the metabolites (hydroxyanastrozole), but it should be taken into account that anastrozole itself inhibits CYP3A495. No influence of potent CYP inducers on anastrozole metabolism is known, and safety data analyses from clinical studies did not show significant interactions with commonly prescribed drugs95.
Managing side effects in adjuvant endocrine therapy for breast cancer
Published in Expert Review of Anticancer Therapy, 2018
Rosaria Condorelli, Ines Vaz-Luis
In 2008, Partridge et al. extended to AIs (in particular anastrozole) their investigations on adherence to ET, using a claimed based cohort from three large commercial health programs with more than 12,000 women diagnosed with early-stage BC. Mean adherence to anastrozole was found to range from 82% to 88% (78% to 86% for those with at least 36 months of continuous follow up) and 62% to 79% over the first and the third year of therapy [25]. In the Intergroup exemestane study, that randomized 4732 patients to exemestane vs. tamoxifen, 15.5% in the exemestane arm and 12.7% in the tamoxifen arm discontinued treatment at 3 years [4]. In the ATAC trial, that randomized 6241 patients to anastrazole vs. tamoxifen, only 76% of the anastrozole group and 72% of the tamoxifen group continued treatment at 47 months after diagnosis [2]. In the combined analysis of TEXT and SOFT trials, that examined 4690 patients assigned to OFS + exemestane and OFS + tamoxifen, 14% of patients in the overall cohort had discontinued ET (16.1% in the OFS + exemestane group and 11.2% in the OFS + tamoxifen group) [13].