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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The results of Phase II clinical trials were disclosed in 1995, and vorozole was reported to be clinically active and well tolerated when given orally for breast cancer. However, the same year, data from a Phase III clinical trial comparing vorozole to the progestational agent megestrol acetate and also aminoglutethimide as second-line therapies in women whose tumors had progressed after treatment with tamoxifen were reported and failed to show a survival advantage, and so further development was halted. A contributing factor was that other aromatase inhibitors such as anastrozole, letrozole, and exemestane were, at the time, providing superior results in the clinic and so the focus shifted to these molecules.
HORMONAL THERAPY OF CANCER
Published in James Bishop, Cancer Facts, 1999
A new group of specific aromatase inhibitors (triazoles) are becoming available, including anastrozole (Arimidex�), letrozole (Femara�), vorozole (Rivizor�). These are potent, pure aromatase inhibitors that are given as a single daily dose and have very few side effects. Early studies suggest they are better tolerated than aminoglutethimide and that they may induce a longer progression-free survival time than progestogens.
Interaction of letrozole and its degradation products with aromatase: chemometric assessment of kinetics and structure-based binding validation
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Michele De Luca, Maria Antonietta Occhiuzzi, Bruno Rizzuti, Giuseppina Ioele, Gaetano Ragno, Antonio Garofalo, Fedora Grande
The emergence and progression of hormone-responsive breast cancer largely depend on the endocrine oestrogenic activity. The treatment of this form of cancer is currently pursued following two main approaches. The first one, more effective during pre-menopausal events when the gonads are the primary producers of oestrogen, is based on the use of antagonists targeting oestrogen receptors. In this case, tamoxifen is the most prescribed drug1. A second approach is preferred in post-menopause, when the production of oestrogen is limited to extra-glandular tissues and consists in the administration of aromatase inhibitors. This enzyme, belonging to the CYP450 superfamily, is expressed in several tissues including gonads, placenta, brain, bone, and adipose tissue. Aromatase acts as a monooxygenase, catalysing the conversion of androgen to oestrogen; thus, its inhibition results in a near complete oestrogen deprivation. Several compounds have been proposed as aromatase inhibitors, leading to a first, second, and third generation of specific agents, the latter being the most prescribed nowadays. Fadrozole and vorozole, which show a non-steroidal structure, were once commonly prescribed but are no longer utilised today, whereas the use of the irreversible steroid inhibitor exemestane is limited to patients pre-treated with tamoxifen in adjuvant therapy2,3.