Nomura Y, Abe O, Tominaga T, Tashiro H, Hisamatsu K, Enomoto K, Fujiwara K, Imoto S, Ando J, Hayashi K
Dept. of Breast Surgery, National Kyushu Cancer Center.
Gan To Kagaku Ryoho. 1994 Feb;21(2):189-97.
Phase I study of CGS16949A--a new aromatase inhibitor--was performed in postmenopausal women with advanced breast cancer who received either single oral administration of 4 and 8 mg, or multiple oral daily administration of 1, 2, 4, 8 and 16 mg for 5.5 days. No side effects were observed after single dose administration of 4 mg and 8 mg of CGS16949A. In the multiple administration, one patient received 1 mg/day for 3 days complained of abdominal pain (Grade 2), but administration of CGS16949 A was continued despite of the pain. In order to assess the causal relationship of the drug with the abdominal pain, the number of patients in 1 mg/day group was doubled from 3 to 6 patients, but no side effects were observed in the remaining five patients. In addition, no side effects, including abdominal pain, were noted in the other 2, 4, 8 and 16 mg/day groups. After multiple administration, plasma concentrations of estradiol at 5 hrs after the final dosage in the respective dose groups were reduced to 47.1 +/- 8.3%, 37.3 +/- 3.0%, 28.0 +/- 7.8%, 26.0 +/- 11.3% and 26.6 +/- 13.8% respectively. Similar tendencies were observed in estrone plasma levels and urinary estrogens levels. In this study, the reduction of plasma estrogen levels was confirmed following administration of CGS 16949A. The clinical usefulness of this new aromatase inhibitor remains to be studied further.
对新型芳香化酶抑制剂CGS16949A进行了I期研究，研究对象为患有晚期乳腺癌的绝经后女性，她们接受了4毫克和8毫克的单次口服给药，或1、2、4、8和16毫克的每日多次口服给药，持续5.5天。单次给予4毫克和8毫克CGS16949A后未观察到副作用。在多次给药中，一名患者连续3天每天服用1毫克，出现腹痛（2级），但尽管疼痛仍继续服用CGS16949A。为了评估药物与腹痛之间的因果关系，将每天1毫克组的患者人数从3名增加一倍至6名，但其余5名患者未观察到副作用。此外，在其他每天2、4、8和16毫克组中未观察到包括腹痛在内的副作用。多次给药后，各剂量组在最后一剂后5小时的雌二醇血浆浓度分别降至47.1±8.3%、37.3±3.0%、28.0±7.8%、26.0±11.3%和26.6±13.8%。雌酮血浆水平和尿雌激素水平也观察到类似趋势。在本研究中，证实了给予CGS 16949A后血浆雌激素水平降低。这种新型芳香化酶抑制剂的临床实用性仍有待进一步研究。
