Addison Christina L, Pond Gregory R, Zhao Huijun, Mazzarello Sasha, Vandermeer Lisa, Goldstein Robyn, Amir Eitan, Clemons Mark
Program for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON Canada ; Department of Medicine, University of Ottawa, Ottawa, ON Canada ; Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON Canada.
Department of Oncology, McMaster University, Hamilton, Canada.
Springerplus. 2014 Oct 1;3:577. doi: 10.1186/2193-1801-3-577. eCollection 2014.
While de-escalation of bisphosphonates from 4 to 12-weekly dosing has been shown to be clinically non-inferior to standard dosing, there is evidence the de-escalation is associated with increased bone turnover biomarkers. Here we evaluated the effect of de-escalated dosing on a panel of biomarkers and determined their association with incidence of skeletal related events (SREs) in breast cancer patients with 'low risk' bone metastases. As part of a pilot randomized trial, women with baseline C-telopeptide levels <600 ng/L after >3 months of 3-4 weekly pamidronate were randomized to continue pamidronate every 4 weeks or de-escalation to 12-weekly treatment. Serum was analysed for bone biomarkers (C-telopeptide, N-telopeptide, bone-specific alkaline phosphatase, transforming growth factor-β, procollagen type 1 N-propeptide, activinA and bone sialoprotein) using ELISA. The associations between changes in biomarkers, pain scores and SREs were assessed by univariable logistic regression. Numerical increases in all biomarkers were observed between baseline and 12 weeks but were of higher magnitude in the de-escalated arm. Pain scores in the de-escalated treatment arm showed a greater magnitude of pain reduction from baseline to 12 weeks. Neither baseline levels nor changes in biomarkers from baseline to 12 weeks on treatment were associated with on study SREs. Baseline pain as measured by the FACT-BP was associated with increased risk of SRE. In conclusion, biomarkers of bone activity do not appear to predict for SREs in 'low risk' cohorts. However, baseline bone pain appears to be associated with SRE occurrence, a finding which warrants evaluation in larger cohorts.
虽然已证明双膦酸盐类药物从每4周给药一次减至每12周给药一次在临床上并不劣于标准给药方案，但有证据表明这种减量与骨转换生物标志物增加有关。在此，我们评估了减量给药对一组生物标志物的影响，并确定了它们与“低风险”骨转移乳腺癌患者骨骼相关事件（SRE）发生率的关联。作为一项试点随机试验的一部分，在接受每3 - 4周一次帕米膦酸治疗超过3个月后基线C - 末端肽水平<600 ng/L的女性被随机分为继续每4周接受帕米膦酸治疗或减量至每12周治疗。使用酶联免疫吸附测定法（ELISA）分析血清中的骨生物标志物（C - 末端肽、N - 末端肽、骨特异性碱性磷酸酶、转化生长因子 - β、I型前胶原N - 端前肽、激活素A和骨唾液蛋白）。通过单变量逻辑回归评估生物标志物变化、疼痛评分与SRE之间的关联。在基线和12周之间观察到所有生物标志物均有数值增加，但在减量组中增加幅度更大。减量治疗组的疼痛评分从基线到12周显示出更大幅度的疼痛减轻。治疗期间从基线到12周的生物标志物基线水平或变化均与研究期间的SRE无关。通过FACT - BP测量的基线疼痛与SRE风险增加相关。总之，骨活性生物标志物似乎不能预测“低风险 ”队列中的SRE。然而，基线骨痛似乎与SRE的发生有关，这一发现值得在更大队列中进行评估。
