乳腺癌骨转移患者骨质调节剂降级
骨质调节剂包括双膦酸盐和地诺单抗（地舒单抗、迪诺舒单抗），通常每4周（标准）给予乳腺癌骨转移患者，以预防骨骼相关事件。最新随机对照研究表明，给药间隔改为每12周（降级）可能疗效相似。
2019年5月11日，施普林格·自然《乳腺癌研究与治疗》在线发表加拿大渥太华医院、渥太华大学、美国密歇根大学的研究报告，通过系统回顾和荟萃分析，比较了乳腺癌骨转移患者骨质调节剂标准与降级给药的利弊。
该研究对Medline、PubMed、Cochrane对照研究登记中心数据库、会议摘要截至2018年3月14日比较骨质调节剂每4周与每12周给药间隔的随机对照临床研究进行检索。按照系统回顾和荟萃分析推荐报告项目（PRISMA）指南，通过随机效应模型进行荟萃分析，结果以风险比和95%置信区间进行报告。
结果，从总共1311篇引文确定8篇全文和1篇摘要，其中包括来自5项已完成随机对照临床研究的1807例数据。
唑来膦酸盐每12周与每4周给药相比：
骨骼事件发生风险相似（汇总风险比：1.05，95%置信区间：0.88～1.25；无论患者是否曾经静脉注射双膦酸盐，结果相似）
肌酐升高发生风险减少（汇总风险比：0.41，95%置信区间：0.15～1.16）
目前，帕米膦酸盐和地诺单抗的降级数据不足。
因此，该荟萃分析数据支持乳腺癌骨转移患者唑来膦酸盐降级。
Breast Cancer Res Treat. 2019 May 11.
De-escalation of bone-modifying agents in patients with bone metastases from breast cancer: a systematic review and meta-analysis.
Awan AA, Hutton B, Hilton J, Mazzarello S, Van Poznak C, Vandermeer L, Bota B, Stober C, Sienkiewicz M, Fergusson D, Shorr R, Clemons M.
The Ottawa Hospital Cancer Centre, Ottawa, Canada; University of Ottawa, Ottawa, Canada; Ottawa Hospital Research Institute, Ottawa, Canada; University of Michigan, Ann Arbor, USA; The Ottawa Hospital, Ottawa, Canada.
PURPOSE: Bone-modifying agents (BMAs) such as bisphosphonates and denosumab are usually administered every 4 weeks (standard) in patients with bone metastases from breast cancer to prevent skeletal-related events (SREs). Recent randomized controlled trials suggest every 12-week (de-escalated) dosing interval may be non-inferior. The objective of this systematic review and meta-analysis was to compare the efficacy and harms of standard with de-escalated administration of BMA's in patients with bone metastases from breast cancer.
METHODS: We searched Medline, PubMed, and the Cochrane Register of Controlled Trials from 1947 to March 14, 2018 and conference abstracts from (2014-March 14, 2018) for randomized clinical trials comparing every 4-week and every 12-week dosing interval of bone-modifying agents. Using PRISMA guidelines, meta-analyses were performed using random-effects models, with findings reported as risk ratios with 95% confidence intervals (CI).
RESULTS: From a total of 1311 citations, we identified 8 full-text articles and 1 abstract comprising data from 5 completed randomized clinical trials (n=1807). Zoledronate administration every 12 weeks compared to every 4 weeks produced a summary risk ratio of 1.05 (95% CI 0.88-1.25) for patients with≥1 on-study SRE indicating similar efficacy. These results did not differ whether patients had received prior intravenous bisphosphonate. De-escalation was associated with a non-statistically significant lower risk of increased creatinine (summary risk ratio 0.41 [95% CI 0.15-1.16]). Currently, there are insufficient data for pamidronate and denosumab de-escalation.
CONCLUSIONS: These data are supportive of de-escalation of zoledronate from onset for patients with bone metastases from breast cancer.
KEYWORDS: Bisphosphonates Denosumab Breast cancer Bone metastasis Skeletal-related event De-escalated treatment
PMID: 31079283
DOI: 10.1007/s10549-019-05265-1