Johnston S R, Smith I E, Doody D, Jacobs S, Robertshaw H, Dowsett M
Breast Unit, Royal Marsden Hospital, London, England.
Cancer Res. 1994 Nov 15;54(22):5875-81.
Vorozole is an orally active, nonsteroidal aromatase inhibitor. Twenty-four postmenopausal patients with advanced breast cancer who had relapsed after treatment with tamoxifen received three separate daily doses of vorozole (1, 2.5, and 5 mg) each for 1 month in a randomized, double-blind, phase II study. There was significant suppression (P < 0.001) of serum estradiol at all three doses (median reduction, 91, 90, and 89%, respectively). There was a significant trend (P = 0.02) for estradiol to be suppressed below the detection limit of the assay (3 pmol/liter) more frequently with an increasing dose of vorozole; 13, 31, and 40% respectively. Estrone and estrone-sulfate levels were likewise reduced at each dose by 52-55% and 64-69%, respectively. There was no significant effect at any dose on aldosterone, testosterone, androstenedione, 17 alpha-hydroxyprogesterone, or thyroid-stimulating hormone levels. A small reduction in cortisol was seen at the 5 mg dose, although the relevance is unclear given that 17 alpha-hydroxyprogesterone levels did not rise. Eight patients (33%) achieved an objective response (2 complete remission, 6 partial remission) with a median response duration of 13 months. Four patients (17%) achieved disease stabilization for more than 6 months. Patients who had responded previously to tamoxifen were more likely to respond to vorozole. There were no significant clinical side effects and the drug was well tolerated. These data suggest that vorozole is a potent and selective oral aromatase inhibitor for use in postmenopausal breast cancer.
伏罗唑是一种口服有效的非甾体类芳香化酶抑制剂。在一项随机、双盲的II期研究中，24例接受他莫昔芬治疗后复发的绝经后晚期乳腺癌患者，分别接受每日3种不同剂量（1毫克、2.5毫克和5毫克）的伏罗唑治疗，每种剂量治疗1个月。所有3种剂量均能显著抑制血清雌二醇（P<0.001）（中位降低率分别为91%、90%和89%）。随着伏罗唑剂量增加，雌二醇被抑制至检测限（3皮摩尔/升）以下的频率有显著趋势（P=0.02）升高；分别为13%、31%和40%。各剂量下雌酮和硫酸雌酮水平同样分别降低52%-55%和64%-69%。各剂量对醛固酮、睾酮、雄烯二酮、17α-羟孕酮或促甲状腺激素水平均无显著影响。5毫克剂量时皮质醇有小幅降低，尽管鉴于17α-羟孕酮水平未升高，其相关性尚不清楚。8例患者（33%）获得客观缓解（2例完全缓解，6例部分缓解），中位缓解持续时间为13个月。4例患者（17%）疾病稳定超过6个月。先前对他莫昔芬有反应的患者更可能对伏罗唑有反应。无显著临床副作用，该药物耐受性良好。这些数据表明伏罗唑是一种用于绝经后乳腺癌的强效且选择性的口服芳香化酶抑制剂。
