Phase II study of CGS16949A, a new aromatase inhibitor--a dose finding study]

A dose finding phase II study of a novel aromatase inhibitor CGS16949A was performed in postmenopausal patients with advanced breast cancer. The daily dose of 1 mg (0.5 mg b.i.d.), 2 mg (1 mg b.i.d.) or 4 mg (2 mg b.i.d.) CGS16949A was administered orally for 8 weeks or more on dose escalation schedule. The response rates (CR+PR) in the evaluable cases were 13.6%, 22.0% and 13.3% in 1 mg/day group (1 mg group), 2 mg/day group (2 mg group) and 4 mg/day group (4 mg group), respectively. There was no statistically significant difference in the response rates among the three treatment groups. Median time to the onset of PR was 99, 113 and 114 days in 1 mg, 2 mg and 4 mg group, respectively, and the median duration of response was 276 days, 391 days and 277 days in 1 mg, 2 mg and 4 mg group, respectively. Five patients in each treatment group showed prolonged stabilization of disease ("long NC", lasting > or = 6 months). Median durations of stabilization were 223 and 241 days in 2 and 4 mg group respectively. The incidence of adverse effects were 11.9%, 7.5% and 13.0% in 1 mg, 2 mg and 4 mg group respectively, and 30 out of 33 symptoms (90.9%) were of mild. Laboratory abnormalities were observed in 12.2%, 22.9% and 23.8% in the respective groups of 1, 2 and 4 mg, and no patient experienced clinical symptoms related to these changes. Plasma estradiol concentration at one month after initiation of the treatment decreased significantly in comparison with pretreatment levels, and was slightly exceeding the limit of detection. Plasma cortisol was not changed. As shown in this results, CGS16949A showed sufficient efficacy and good tolerability in postmenopausal patients with advanced breast cancer. It was considered that the optimal dose in clinical use judged as 2 mg/day.