The role of tamoxifen and aromatase inhibitors/inactivators in postmenopausal patients.
The traditional hormonal cascade of the 1970s and 1980s used tamoxifen followed by megestrol acetate and subsequently by aminoglutethimide. In the 1990s, however, three trials of third-generation aromatase inhibitors (AIs) compared with megestrol acetate and two trials of third-generation AIs compared with aminoglutethimide showed improved efficacy and decreased toxicity for the newer AIs. Thus, the hormonal cascade changed in the late 1990s, to one in which tamoxifen, followed by a third-generation AI, followed by megestrol acetate, seemed more suitable. Now, however, several trials comparing anastrozole, letrozole, and exemestane to tamoxifen as first-line hormonal agents for metastatic breast cancer have shown that these drugs are at least equivalent and perhaps superior to tamoxifen in that setting in terms of response rate and time to progression. Results from 1021 patients randomized to receive anastrozole versus tamoxifen showed a slightly improved overall response rate (RR; 29% versus 26%), slightly improved clinical benefit (CB; 57% versus 52%), and a significantly improved time to progression (TTP; 8.5 months versus 7.0 months) in favor of anastrozole. In 907 women randomized to treatment with letrozole versus tamoxifen, significantly improved RR (30% versus 20%), CB (49% versus 38%), and TTP (9.4 months versus 6 months) have all been shown for those treated with letrozole. In addition, a randomized Phase II trial of 121 patients has shown nonsignificant benefits in favor of exemestane (RR 41% versus 14%; CB 56% versus 42%; TTP not available). To date, none of these trials has demonstrated any overall survival benefit. Additional follow-up in regard to survival in the trial of tamoxifen versus letrozole and an expanded Phase III trial of tamoxifen versus exemestane are ongoing.
Pritchard
K I
KI
Toronto-Sunnybrook Regional Cancer Centre, University of Toronto, Ontario, Canada. kathy.pritchard@tsrcc.on.ca
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D017698:Postmenopause; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D013629:Tamoxifen / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D013629:Tamoxifen