Bonnefoi H R, Smith I E, Dowsett M, Trunet P F, Houston S J, da Luz R J, Rubens R D, Coombes R C, Powles T J
Royal Marsden Hospital and Institute of Cancer Research, London, UK.
Br J Cancer. 1996 Feb;73(4):539-42. doi: 10.1038/bjc.1996.93.
The endocrine and therapeutic effects of the aromatase inhibitor fadrozole hydrochloride have been assessed in 80 post-menopausal patients with recurrent breast cancer after tamoxifen failure. Treatment allocation was randomly 0.5, 1.0 or 2.0 mg orally b.d. Eight patients were not assessable for response. All patients were evaluated for toxicity (intent-to-treat analysis). In general, the patients' characteristics were well balanced between the three randomised groups. The endocrine data from this study previously reported suggest a dose-related suppression of oestrone, but not oestradiol or oestrone sulphate. The objective response rate was 17% (95% CI 8.9-27.3%) with no complete responders. Fifteen patients (21%) had stable disease (NC) and 45 patients (63%) had progressive disease (PD). The median duration of objective response was 36 weeks. The median time to treatment failure was 12.7 weeks. The log-rank test showed no statistical difference between the dosage groups. The main adverse events reported were mild to moderate severity: nausea in 11 patients (15%), hot flashes in four (5%) and somnolence in three (4%). No serious adverse events were reported. In conclusion, fadrozole is a clinically active aromatase inhibitor with a low incidence of side-effects and phase III clinical trials in post-menopausal women are currently under way.
已在80例他莫昔芬治疗失败的绝经后复发性乳腺癌患者中评估了芳香化酶抑制剂盐酸法倔唑的内分泌和治疗效果。治疗分配为随机口服0.5、1.0或2.0mg，每日两次。8例患者无法评估反应。对所有患者进行毒性评估（意向性治疗分析）。总体而言，三个随机分组之间患者的特征平衡良好。此前报道的该研究的内分泌数据表明，雌激素酮受到剂量相关的抑制，但雌二醇或硫酸雌酮未受影响。客观缓解率为17%（95%CI 8.9 - 27.3%），无完全缓解者。15例患者（21%）病情稳定（NC），45例患者（63%）病情进展（PD）。客观缓解的中位持续时间为36周。治疗失败的中位时间为12.7周。对数秩检验显示剂量组之间无统计学差异。报告的主要不良事件为轻度至中度：11例患者（15%）出现恶心，4例（5%）出现潮热，3例（4%）出现嗜睡。未报告严重不良事件。总之，法倔唑是一种具有临床活性的芳香化酶抑制剂，副作用发生率低，目前正在绝经后妇女中进行III期临床试验。
