Wiseman L R, Adkins J C
Adis International Limited, Auckland, New Zealand.
Drugs Aging. 1998 Oct;13(4):321-32. doi: 10.2165/00002512-199813040-00008.
Anastrozole is a new oral nonsteroidal aromatase inhibitor indicated for the second-line endocrine treatment of postmenopausal women with advanced breast cancer. In postmenopausal women, anastrozole significantly reduces plasma estrogen levels; maximal suppression is achieved at dosages > or = 1 mg/day and levels remain suppressed during long term therapy. In two phase III clinical trials, anastrozole 1 or 10 mg/day showed similar clinical efficacy to that of oral megestrol (megestrol acetate) 160 mg/day in postmenopausal women with advanced breast cancer. Primary end-points [including time to disease progression (120 to 170 days) and overall response rates (complete and partial response and stable disease lasting > or = 24 weeks: 29 to 37%)] and secondary end-points [time to treatment failure (115 to 168 days) and duration of response (257 to 261 days)] did not differ significantly between treatment groups. However, a significant survival advantage was observed in patients treated with anastrozole 1 mg/day compared with megestrol in a follow-up combined analysis of patients enrolled in both studies (median time to death 26.7 vs 22.5 months). Quality of life parameters were generally improved to a similar extent in all treatment groups. Anastrozole is generally well tolerated in the majority of patients, the most common adverse events being gastrointestinal (GI) disturbances (incidence 29 to 33%). These events are generally mild or moderate and transient. Other adverse events reported with anastrozole include headache (< or = 18%), asthenia (< or = 16%), pain (< or = 15%), hot flushes and bone pain (both < or = 12%), back pain and dyspnoea (both < or = 11%) and peripheral oedema (< or = 9%). GI disturbance tended to be more common with anastrozole than megestrol, particularly at the 10 mg/day dosage; however, compared with megestrol, anastrozole is less frequently associated with weight gain.
Anastrozole, with its apparent survival advantage versus megestrol (demonstrated in a combined analysis of phase III studies), convenient once daily oral administration and acceptable short term tolerability profile, is a second-line treatment option for postmenopausal patients with tamoxifenrefractory advanced breast cancer. The results of ongoing comparative trials with tamoxifen will determine the relative efficacy of anastrozole as first-line endocrine therapy for advanced breast cancer and as adjuvant therapy for early disease. In addition, direct comparative studies are required to determine the efficacy of anastrozole relative to that of other oral aromatase inhibitors such as letrozole and vorozole.
阿那曲唑是一种新型口服非甾体类芳香化酶抑制剂，适用于绝经后晚期乳腺癌女性的二线内分泌治疗。在绝经后女性中，阿那曲唑可显著降低血浆雌激素水平；剂量≥1mg/天时可实现最大抑制效果，且在长期治疗期间水平持续受到抑制。在两项III期临床试验中，对于绝经后晚期乳腺癌女性，阿那曲唑1mg/天或10mg/天显示出与口服醋酸甲地孕酮160mg/天相似的临床疗效。主要终点指标[包括疾病进展时间（120至170天）和总缓解率（完全缓解、部分缓解以及疾病稳定持续≥24周：29%至37%）]和次要终点指标[治疗失败时间（115至168天）和缓解持续时间（257至261天）]在各治疗组之间无显著差异。然而，在两项研究中纳入患者的随访联合分析中，与甲地孕酮相比，接受阿那曲唑1mg/天治疗的患者观察到显著的生存优势（中位死亡时间26.7个月对22.5个月）。所有治疗组的生活质量参数总体上均有类似程度的改善。阿那曲唑在大多数患者中通常耐受性良好，最常见的不良事件为胃肠道紊乱（发生率为29%至33%）。这些事件一般为轻度或中度且为短暂性。阿那曲唑报告的其他不良事件包括头痛（≤18%）、乏力（≤16%）、疼痛（≤15%）以及潮热和骨痛（均≤12%）、背痛和呼吸困难（均≤11%）以及外周水肿（≤9%）。胃肠道紊乱在阿那曲唑治疗组中往往比甲地孕酮治疗组更常见，尤其是在10mg/天剂量时；然而，与甲地孕酮相比，阿那曲唑与体重增加的相关性较低。
阿那曲唑与甲地孕酮相比具有明显的生存优势（在III期研究的联合分析中得到证实），每日一次口服给药方便且短期耐受性可接受，是他莫昔芬难治性绝经后晚期乳腺癌患者的二线治疗选择。正在进行的与他莫昔芬的对比试验结果将确定阿那曲唑作为晚期乳腺癌一线内分泌治疗以及早期疾病辅助治疗的相对疗效。此外还需要进行直接对比研究以确定阿那曲唑相对于其他口服芳香化酶抑制剂如来曲唑和伏罗唑的疗效。
