Iveson T J, Smith I E, Ahern J, Smithers D A, Trunet P F, Dowsett M
Breast Unit, Royal Marsden Hospital, London, England.
Cancer Res. 1993 Jan 15;53(2):266-70.
A phase I study was performed of CGS 20267, an oral nonsteroidal, highly potent, and selective aromatase inhibitor, in 21 postmenopausal patients with advanced breast cancer. The patients were recruited in 3 successive groups of 7, receiving 0.1, 0.5, and 2.5 mg p.o./day, respectively. All patients had received at least one prior endocrine treatment (range, 1-4), and six patients had received prior chemotherapy. The treatment was very well tolerated, and no toxicity was seen at any of the three doses. There was a statistically significant suppression of estradiol (E2) and estrone (E1) levels by 74% and 79% from baseline levels, respectively (P < 0.0001). Suppression occurred in all three patient groups, with many patients having serum concentrations of estradiol and estrone, which were below the limit of detection of the assays (3 and 10 pM, respectively), which corresponds to a maximum measurable estrogen suppression of 86%. CGS 20267 had no significant effect on serum levels of follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, cortisol, 17 alpha-hydroxyprogesterone, androstenedione, and aldosterone. Seven (33%, 95% confidence interval, 15-57%) of the 21 patients have responded to treatment (one complete remission, 6 partial remissions according to criteria of the Union Internationale contre le Cancer), and 6 are still responding to CGS 20267 (duration of response; 4+, 6+, 6+, 9+, 9, 12+, and 12+ months). Five have had stable disease for more than 3 months, and 9 had progressive disease. These results suggest that CGS 20267 is a very potent and specific aromatase inhibitor, and phase II studies are now required to confirm its clinical efficacy.
对21例绝经后晚期乳腺癌患者进行了CGS 20267（一种口服非甾体、高效且选择性的芳香化酶抑制剂）的I期研究。患者被连续分为3组，每组7例，分别接受0.1、0.5和2.5mg/天的口服给药。所有患者至少接受过一种先前的内分泌治疗（范围为1 - 4种），6例患者接受过先前的化疗。治疗耐受性良好，三种剂量均未观察到毒性。雌二醇（E2）和雌酮（E1）水平分别较基线水平有统计学意义的显著降低，降幅分别为74%和79%（P < 0.0001）。所有三组患者均出现抑制，许多患者的雌二醇和雌酮血清浓度低于检测限（分别为3和10pM），这相当于最大可测量雌激素抑制率为86%。CGS 20267对血清促卵泡激素、促黄体生成素、促甲状腺激素、皮质醇、17α - 羟孕酮、雄烯二酮和醛固酮水平无显著影响。21例患者中有7例（33%，95%置信区间，15 - 57%）对治疗有反应（1例完全缓解，6例根据国际抗癌联盟标准为部分缓解），6例仍对CGS 20267有反应（反应持续时间；4 +、6 +、6 +、9 +、9、12 +和12 +个月）。5例病情稳定超过3个月，9例病情进展。这些结果表明CGS 20267是一种非常强效且特异性的芳香化酶抑制剂，现在需要进行II期研究以证实其临床疗效。
