[Current status and prospectives of aromatase inhibitors in the treatment of advanced breast cancer].
Endocrine therapy represents one of the most effective instruments for the palliative and adjuvant treatment of breast cancer, in particular in postmenopausal patients. While tamoxifen still forms the treatment of choice during the adjuvant phase and the first-line treatment during the metastatic phase, aromatase inhibitors undoubtedly represent the treatment of choice for patients who do not respond to antiestrogen treatment. These drugs represent a heterogeneous family of compounds able to provide more or less selective inhibition of aromatases by forming an irreversible bond with the catalytic site of the enzymatic complex (type I inhibitors) or using a competitive mechanism (type II inhibitors). Among the type I drugs, 4-hydroxyandrostenedione and hexamestane are those that probably attract greatest clinical interest. These drugs can significantly reduce the circulating levels of estrone and estradiol, and have been shown to be active in 20% of patients pretreated with tamoxifen. Moreover, hexamestane was also effective in patients pretreated with type II inhibitors, of which the parent drug is aminoglutethimide. This drug is still used in the second and third-line treatment of breast cancer but, since it causes collateral effects in a substantial percentage of patients, above all when used at higher doses in combination with hydrocortisone, it will soon be replaced by second and third generation inhibitors, like letrozole, fadrozole, vorozole and anastrozole. These drugs have been shown to be significantly more active than aminoglutethimide, both in vitro and in vivo, and above all more selective. In particular, even at high doses anastrozole has not been found to interfere with steroidogenesis at a corticoadrenal level. Moreover, anastrozole has been shown to be very active even at relatively modest doses given in a single daily dose. Two recent controlled studies, including a total of over 600 patients, recently demonstrated that, if used in second line in patients who no longer responded to adjuvant or palliative tamoxifen therapy, anastrozole is just as effective but probably better tolerated than megestrol acetate. Studies are now in progress or are currently being launched to evaluate the possible value of anastrozole and other third generation inhibitors both as first-line treatment and as adjuvant treatment as an alternative or in combination with tamoxifen.
Boccardo
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Servizio di Oncologia Medica II, Istituto Nazionale per la Ricerca sul Cancro, Genova.
D001141:Aromatase / Q000627:therapeutic use; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D013629:Tamoxifen / Q000627:therapeutic use*
D047072:Aromatase Inhibitors; D013629:Tamoxifen; D001141:Aromatase
Stato attuale e prospettive nel trattamento del carcinoma mammario avanzato con gli inibitori dell'aromatasi.