[Phase I study of TAT-59 (a new antiestrogen) in breast cancer. TAT-59 Study Group]

Phase I study of TAT-59 (Miproxifen), an antiestrogen developed in Japan for breast cancer, was conducted with the collaboration of 12 hospitals. A single dose of 1.25, 5, 10, 20, 40 and 80 mg, or 5 consecutive daily doses of 1.25, 5, 10, 20 and 40 mg/day, were given orally. After single dosing, no clinical adverse effects were found. Decrease of serum Na, Cl, Ca level and increase of serum LDH level were observed in one patient after a single dose of 5 mg of TAT. An increase in the serum LDH level was also observed in one patient after a single dose in the of 10 mg of TAT. An increase in the serum LDH level and total bilirubin, increase of eosinophil, K and milky serum were also observed in one patient after a single dose of 40 mg of TAT, respectively. All of these abnormal values returned to the normal level within 26 days after final administration of TAT. No adverse clinical findings nor abnormal laboratory findings were observed after consecutive administration of TAT. After postprandial single dosing, the time to reach the maximum serum concentration (Tmax) of DP-TAT, dephosphorylated metabolite of TAT, and its demethylated metabolite, DMDP, ranged from 5.0 to 7.3 hr and from 17.0 to 42.8 hr, respectively. The maximum serum concentration (Cmax) and AUC of DP and DMDP elevated in a dose-dependent manner. T1/2 of DP and DMDP ranged from 24.2 to 41.5, and from 91.9 to 214.7 hr, respectively. There were no significant differences between pharmacokinetics of TAT before and after food intake. Based on the above results, we concluded that a Phase II study should be conducted to evaluate the efficacy, safety and optimal dose of TAT.