Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer
Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer
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DOI：
10.1007/s10549-011-1429-y
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发表时间：
2011-06-01
影响因子：
3.8
通讯作者：
Thorpe, H.
中科院分区：
文献类型：
--
作者：
Coleman, R.;Woodward, E.;Thorpe, H.
AZURE试验是一项正在进行的III期、学术性、多中心、随机试验，旨在评估唑来膦酸（ZOL）在II/III期乳腺癌女性辅助治疗中的作用。在这里，我们报告了ZOL在这种情况下的安全性和耐受性。合格患者接受（新）辅助化疗和/或内分泌治疗，并随机分配至不接受额外治疗或静脉注射ZOL 4 mg。在每个化疗周期后给予ZOL以利用潜在的序列依赖性协同作用。ZOL在随机化后持续60个月（前6个月6剂，随后24个月8剂，最后30个月5剂）。分析了安全性人群在研究前36个月内生成的严重（SAE）和非严重不良事件（AE）数据。AZURE试验招募了3，360名患者。安全性人群包括3，340例患者（ZOL 1，665例;对照1，675例）。在标准治疗中添加ZOL对化疗输送没有显著影响。两个治疗组的SAE相似。除了ZOL组中发生颌骨坏死（ONJ）外，未观察到显著的安全性差异（11例确诊病例; 0.7%; 95%置信区间0.3 - 1.1%）。ZOL在辅助治疗中的耐受性良好，并且除了辅助治疗（包括化疗）之外还可以安全地给药。不良事件与ZOL已知的安全性特征一致，ONJ的发生率较低。
The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3-1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.