TY - JOUR
T1 - New generation aromatase inhibitors - From the advanced to the adjuvant setting
AU - Buzdar, Aman U.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2002/10
Y1 - 2002/10
N2 - Aromatase inhibitors (AIs) are a class of compounds that inhibit the cytochrome P450 aromatase enzyme that mediates conversion of androgens to estrogen in the adrenal gland. AIs have been approved for second-line and, more recently, first-line treatment of advanced breast cancer in postmenopausal women. The most recent, third generation of AIs are the non-steroidal agents anastrozole ('Arimidex') and letrozole, and the steroidal compound exemestane. As second-line therapy, anastrozole demonstrated a significant survival advantage over megestrol acetate (26.7 months v.s. 22.5 months; p < 0.025). Exemestane also produced better survival than megestrol acetate, although these data were less mature. Letrozole 2.5 mg has not demonstrated a survival advantage versus megestrol acetate in the second-line setting. As first-line therapy, anastrozole has demonstrated significant superiority in response rates with respect to time to progression (TTP) (11.1 months v.s. 5.6 months; p = 0.005) and has also demonstrated significantly greater clinical benefit rates compared with tamoxifen (59.1% v.s. 45.6%; p = 0.0098). Letrozole has also demonstrated significantly longer TTP than tamoxifen in the first-line setting (9.5 months v.s. 6 months; p = 0.0001). Important differences between the pharmacological profiles of these agents have been noted, particularly with respect to their effects on glucocorticoid metabolism; data for individual agents should not be extrapolated from one to another, particularly in the adjuvant setting.
AB - Aromatase inhibitors (AIs) are a class of compounds that inhibit the cytochrome P450 aromatase enzyme that mediates conversion of androgens to estrogen in the adrenal gland. AIs have been approved for second-line and, more recently, first-line treatment of advanced breast cancer in postmenopausal women. The most recent, third generation of AIs are the non-steroidal agents anastrozole ('Arimidex') and letrozole, and the steroidal compound exemestane. As second-line therapy, anastrozole demonstrated a significant survival advantage over megestrol acetate (26.7 months v.s. 22.5 months; p < 0.025). Exemestane also produced better survival than megestrol acetate, although these data were less mature. Letrozole 2.5 mg has not demonstrated a survival advantage versus megestrol acetate in the second-line setting. As first-line therapy, anastrozole has demonstrated significant superiority in response rates with respect to time to progression (TTP) (11.1 months v.s. 5.6 months; p = 0.005) and has also demonstrated significantly greater clinical benefit rates compared with tamoxifen (59.1% v.s. 45.6%; p = 0.0098). Letrozole has also demonstrated significantly longer TTP than tamoxifen in the first-line setting (9.5 months v.s. 6 months; p = 0.0001). Important differences between the pharmacological profiles of these agents have been noted, particularly with respect to their effects on glucocorticoid metabolism; data for individual agents should not be extrapolated from one to another, particularly in the adjuvant setting.
KW - Advanced breast cancer
KW - Anastrozole
KW - Aromatase inhibitors
KW - Estrogen receptor
KW - Postmenopausal
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U2 - 10.1023/a:1020305615033
DO - 10.1023/a:1020305615033
M3 - Review article
C2 - 12353818
AN - SCOPUS:0036776751
SN - 0167-6806
VL - 75
SP - S13-S17
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - SUPPL. 1
ER -