LETROZOLE, A NEW ORAL AROMATASE INHIBITOR FOR ADVANCED BREAST-CANCER - DOUBLE-BLIND RANDOMIZED TRIAL SHOWING A DOSE-EFFECT AND IMPROVED EFFICACY AND TOLERABILITY COMPARED WITH MEGESTROL-ACETATE
P. Dombernowsky et al., LETROZOLE, A NEW ORAL AROMATASE INHIBITOR FOR ADVANCED BREAST-CANCER - DOUBLE-BLIND RANDOMIZED TRIAL SHOWING A DOSE-EFFECT AND IMPROVED EFFICACY AND TOLERABILITY COMPARED WITH MEGESTROL-ACETATE, Journal of clinical oncology, 16(2), 1998, pp. 453-461
Purpose: to compare two doses of letrozole and megestrol acetate (MA)
as second-line therapy in postmenopausal women with advanced breast ca
ncer previously treated with antiestrogens. Patients and Methods: Five
hundred fifty-one patients with locally advanced, locoregionally recu
rrent or metastatic breast cancer were randomly assigned to receive le
trozole 2.5 mg (n = 174), letrozole 0.5 mg (n = 188), or MA 160 mg (n
= 189) once daily in a double-blind, multicenter trial. Data were anal
yzed for tumor response and safety variables vp to 33 months of follow
-up evaluation and for survival vp to 45 months. Results: Letrozole 2.
5 mg produced a significantly higher overall objective response rate (
24%) compared with MA (16%; logistic regression, P = .04) or letrozole
0.5 mg (13%; P = .004). Duration of objective response was significan
tly longer for letrozole 2.5 mg compared with MA (Cox regression, P =
.02). Letrozole 2.5 mg was significantly superior to MA and letrozole
0.5 mg in time to treatment failure (P = .04 and P = .002, respectivel
y). For time to progression, letrozole 2.5 mg was superior to letrozol
e 0.5 mg (P = .02), but not to MA (P = .07). There was a significant d
ose effect in overall survival in favor of letrozole 2.5 mg (P = .03)
compared with letrozole 0.5 mg. Letrozole was significantly better tol
erated than MA with respect to serious adverse experiences, discontinu
ation due to poor tolerability, cardiovascular side effects, and weigh
t gain. Conclusion: The data show letrozole 2.5 mg once daily to be mo
re effective and better tolerated than MA in the treatment of postmeno
pausal women with advanced breast cancer previously treated with antie
strogens. (C) 1998 by American Society of Clinical Oncology.