Henoch–Schönlein purpura (HSP) during treatment with anastrozole (original) (raw)
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Aromatase inhibitors and their future role in post-menopausal women with early breast cancer
British journal of cancer, 1998
Anastrozole is the first aromatase inhibitor to show a significant survival advantage over megestrol acetate in post-menopausal women with advanced breast cancer. The rationale for extending the use of aromatase inhibitors to the treatment of early breast cancer is based on the efficacy observed in the advanced setting, combined with good tolerability and a convenient dosing regimen. Furthermore, oestrogen deprivation by ovarian ablation (similar to oestrogen antagonism with tamoxifen) is already established as an effective adjuvant treatment in premenopausal women with modality breast cancer. Anastrozole produces a profound suppression of plasma oestrogen levels which is greater than that obtained with earlier aromatase inhibitors (formestane, aminoglutethimide) or megestrol acetate. This could account for the differences in clinical efficacy seen between anastrozole and megestrol acetate. In terms of benefits over other endocrine agents, anastrozole causes significantly less weigh...
Aromatase Inhibitors for Breast Cancer in Postmenopausal Women
2004
Third-generation aromatase inhibitors are potent inhibitors of the aromatase enzyme, which catalyzes the last step in estrogen biosynthesis. These agents are active against breast cancer in hormone-naïve postmenopausal women and in women who have experienced failure of tamoxifen or failure of tamoxifen plus other hormonal therapy. There are two types of aromatase inhibitors, irreversible steroidal activators (e.g., exemestane) and reversible nonsteroidal imidazole-based inhibitors (e.g., anastrozole, letrozole). Recent data suggest that some women who experience failure of one type of aromatase inhibitor can subsequently derive benefit from the other type. The reason for this lack of cross-resistance is unknown. This finding of non-cross-resistance between steroidal aromatase activators and nonsteroidal aromatase inhibitors offers the opportunity to increase the number of lines of hormone therapy before making the inevitable switch to more toxic chemotherapy, thus potentially improving quality of life for postmenopausal women with advanced disease.
Third-generation aromatase inhibitors in the treatment of advanced breast cancer
Breast Cancer, 2001
Endocrine therapy has been used for the treatment of advanced breast cancer for more than a hundred years. While ovarian ablation was previously the mainstay of therapy, in the last three decades most effort has focused on developing novel agents that deprive tumor cells of estrogen stimulation. Currently available drugs either antagonize the effects of estrogen on tumor cells by blocking hormone interaction with the estrogen receptor, or inhibit the conversion of androgens to estrogen.
Aromatase inhibitors in the treatment of early and advanced breast cancer
Acta Oncologica, 2005
The third generation aromatase inhibitors anastrozole, exemestane, and letrozole have been compared with tamoxifen and other endocrine therapies in several studies in early and advanced breast cancer. These studies are reviewed in this report. Based on the available evidence, the panel recommends that adjuvant treatment with tamoxifen for 5 years should no longer be considered as the sole standard but that a third-generation aromatase inhibitor should be used either alone or in a sequence with tamoxifen in the adjuvant treatment of postmenopausal women with hormone-receptor-positive breast cancer. Third generation aromatase inhibitors may be considered as the first line therapy of hormone-receptor-positive advanced breast cancer in postmenopausal women, and they may also be used for preoperative therapy of breast cancer.
Aromatase Inhibitors in advanced breast cancer
2010
A number of potent and selective non-steroidal aromatase inhibitors are now available for treatment of advanced breast cancer in postmenopausal women, of which anastrozole and letrozole, in particular, represent a significant advantage over the earlier agents in terms of both efficacy and tolerability. These agents are rapidly becoming established as the second-line therapy of choice in postmenopausal women with advanced disease, progressing on tamoxifen, and data on their efficacy as first-line treatment compared with tamoxifen will be available in the near future. Exemestane, a new, steroidal aromatase inhibitor which potentially lacks cross-resistance with non-steroidal agents is still in clinical development. The full potential of the new-generation aromatase inhibitors in the treatment of breast cancer is currently being investigated in a large program of clinical trials evaluating their use Endocrine-Related Cancer (1999) 6 219-225 as adjuvant treatment following surgery in postmenopausal patients with early disease.
Therapeutic effects of the aromatase inhibitor fadrozole hydrochloride in advanced breast cancer
British journal of cancer, 1996
The endocrine and therapeutic effects of the aromatase inhibitor fadrozole hydrochloride have been assessed in 80 post-menopausal patients with recurrent breast cancer after tamoxifen failure. Treatment allocation was randomly 0.5, 1.0 or 2.0 mg orally b.d. Eight patients were not assessable for response. All patients were evaluated for toxicity (intent-to-treat analysis). In general, the patients' characteristics were well balanced between the three randomised groups. The endocrine data from this study previously reported suggest a dose-related suppression of oestrone, but not oestradiol or oestrone sulphate. The objective response rate was 17% (95% CI 8.9-27.3%) with no complete responders. Fifteen patients (21%) had stable disease (NC) and 45 patients (63%) had progressive disease (PD). The median duration of objective response was 36 weeks. The median time to treatment failure was 12.7 weeks. The log-rank test showed no statistical difference between the dosage groups. The m...
Anastrozole Use in Early Stage Breast Cancer of Post-Menopausal Women
Clinical medicine. Therapeutics, 2009
The majority of breast cancers express the estrogen receptor and depend on estradiol (E2) for their growth. Hormonal therapy aims at depriving estrogen signaling either by using selective estrogen receptor modulators (SERM)-that interfere with the binding of E2 to its receptor (ER)-or aromatase inhibitors (AI)-that block the aromatase-dependent synthesis of E2. While SERMs are recommended for both pre- and post-menopausal patients, AIs are indicated only for post-menopausal patients. For the past 20 years, the SERM tamoxifen has been considered the "gold standard" for the treatment of hormone receptor positive breast cancers. However, tamoxifen's role is now challenged by third generation AIs, such as anastrozole, which exhibit greater efficacy in the adjuvant setting in several recently reported trials. This review will focus on anastrozole's mechanism of action, dosing, pharmacology, pharmacokinetics, and clinical applications. It will briefly discuss the clinica...
British journal of cancer, 1996
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. Treatment with anastrozole 1 and 10 mg reduced the percentage aromatisation from 2.25% to 0.074% and 0.043% (mean suppression of 96.7% and 98.1% from baseline) and suppressed plasma levels of oestrone, oestradiol and oestrone sulphate by > or = 86.5%, > or = 83.5% and > or = 93.5% respectively, irrespective of dose. Notably, several patients had their oestrone and oestradiol values suppressed beneath the sensitivity limit of the assays. In conclusion,...
Aromatase inhibitors in breast cancer
The American Journal of Geriatric Pharmacotherapy, 2004
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.