373 Phase II trial of letrozole (a novel oral nonsteroidal aromatase inhibitor) in postmenopausal patients with advanced or recurrent breast cancer

Abstract

64 Japanese postmenopausal patients (pts) (median age 59: range 38–76) with advanced or recurrent breast cancer who had received more than 1 prior regimen (honnonotherapy and/or chemotherapy) were randomized between 2 oral regimen of letrozole for more than 8 weeks, 33 pts (ER+: 18, ER−: 3, unknown: 12) being given 0.5 mg of letrozole daily and 31 pts (ER+: 15, ER−: 3, unknown: 13), 1 mg daily. The tumor responses were peer reviewed and response rates (CR + PR in evaluable cases were 28% (3CR + 6PR/32, 95% C.I.: 14–47%) in 0.5 mg group and 39% (5CR + 6PR/28, 95% C.I.: 22–59%) in the 1 mg group, respectively. Stabilization of the disease for more than 6 months (long NC) was obtained in 19% for the 0.5 mg group and in 29% for the 1 mg group, respectively. Progressive disease was noted in 31% for the 0.5 mg group and in 21% for the 1 mg group, respectively. Clinical adverse experiences were observed in 6% of pts (2/33, 5 events) for the 0.5 mg group and in 6% of pts (2/31, 2 events) for the 1 mg group, all being only of mild severity (grade 1) except one event of grade 2 itching in the 1 mg group. Laboratory test abnonnalities were found in 9% of pts (3/33,6 events) for the 0.5 mg group and in 10% of pts (3/31, 6 events) for the 1 mg group, respectively. Except for one event of grade 2 GOT and GPT elevation noted in the 0.5 mg group, all other events were of either grade 0 or grade 1 severity. Estrone levels were maintained below the detection limit (2.5 pg/ml) and a sustained estradiol suppression was observed, with levels near the detection limit (1 pg/ml) during treatment. There was no clinically relevant changes in the other hormones (aldosterone, cortisol, FSH, LH, testostetone, androstenedione). These highly promising results support further extensive clinical evaluation.