Endoxifen: The End, or Are We at the Beginning?
Mené sur 41 patientes atteintes d'un cancer du sein ER+ de stade métastatique et réfractaire à une hormonothérapie, cet essai de phase I évalue l'activité antitumorale, les caractéristiques pharmacocinétiques, la toxicité et la dose maximale tolérée du Z-endoxifène, un métabolite du tamoxifène
Tamoxifen had its origins as a failed morning-after contraceptive that became the first successful targeted treatment in cancer.1-3 Tamoxifen dominated the antiestrogenic treatment of metastatic breast cancer (MBC) for 30 years and went forward as the only candidate for long-term adjuvant antiestrogen treatment.2,3 As a result of decades of clinical testing, tamoxifen was the only candidate in the pioneering of breast cancer chemoprevention.4 There was a reason for this. Try as they may, medicinal chemists in the pharmaceutical industry could not improve on tamoxifen for the treatment of MBC. The list of nonsteroidal antiestrogens evaluated to treat MBC is long: nafoxidine, trioxifene, keoxifene (reinvented and renamed raloxifene to treat osteoporosis5), toremifene, droloxifene, and arzoxifene.6,7 As a result, an alternative strategy for antiestrogen therapy was advanced. Specific inhibitors of CYP19, the aromatase enzyme, were investigated. In the 1970s, Dr Angela Brodie, the mother of aromatase inhibitors (AIs), used translational research to show that a clinically useful drug was possible.8 The pharmaceutical industry again struggled for a decade to find suitable oral candidates to compete with tamoxifen. Today, there are three established agents that dominate breast cancer treatment and prevention for postmenopausal women: anastrozole, exemestane, and letrozole. So it comes as some surprise that a phase I study of endoxifen, a tamoxifen metabolite, was successfully completed in patients with endocrine refractory breast cancer (...)