One-Day Versus Three-Day Dexamethasone in Combination with Palonosetron for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Individual Patient Data-Based Meta-Analysis
One-Day Versus Three-Day Dexamethasone in Combination with Palonosetron for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Individual Patient Data-Based Meta-Analysis
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DOI：
10.1634/theoncologist.2019-0133
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发表时间：
2019-12-01
期刊：
影响因子：
5.8
通讯作者：
Aapro, Matti
中科院分区：
文献类型：
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作者：
Okada, Yuki;Oba, Koji;Aapro, Matti
背景：地塞米松保留方案包括帕洛诺司琼加地塞米松1天预防化疗引起的恶心和呕吐（CINV）以前已经研究过。在这里，我们使用基于个体患者数据（IPD）的荟萃分析来评估地塞米松保留方案在总体止吐控制方面的非劣效性。材料和方法我们对报告CINV结果的随机试验进行了系统回顾，以比较帕洛诺司琼加1天地塞米松（d1组）与化疗后2-3天地塞米松（d3组）的相同方案。接受中度致吐化疗（MEC）或含蒽环类药物加环磷酰胺（AC）化疗的初治成人患者。电子检索PubMed和MEDLINE。还进行了人工搜索。主要终点是整个5天研究期间的完全缓解（CR;无呕吐和无补救药物）。非劣效性界值设定为-8.0%（d1组-d3组）。结果5项研究（n = 1，194）符合分析条件，收集了所有IPD。在整个研究期间，d1组显示CR和完全控制非劣效于d3组（CR率的合并风险差异-1.5%，95%置信区间[CI] -7.1至4.0%，I-2 = 0%;完全控制率-2.4%，95% CI -7.7至2.9%，I-2 = 0%）。地塞米松治疗方案与危险因素之间无明显交互作用结论IPD荟萃分析表明，在接受MEC或AC化疗的患者中，地塞米松保留方案与总体止吐控制的显著损失无关，而不考虑已知的CINV的危险因素。实践的意义尽管地塞米松与其它止吐剂联合用于预防化疗引起的恶心和呕吐（CINV），在接受多周期致吐化疗的患者中，最小化地塞米松的总剂量具有临床重要性。这项来自5项随机对照试验（1，194例患者）的个体患者数据荟萃分析证明了地塞米松保留方案在CINV完全缓解和完全控制方面的非劣效性。具有不同特征的患者的结局具有可比性。因此，这些发现有助于医生最大限度地减少类固醇的使用，并进一步减少接受多个连续疗程致吐化疗的患者的地塞米松相关副作用的负担。
Background A dexamethasone-sparing regimen consisting of palonosetron plus 1-day dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) has been studied previously. Here, we evaluate the noninferiority of the dexamethasone-sparing regimen in overall antiemetic control using a meta-analysis based on individual patient data (IPD).Materials and Methods We conducted a systematic review for randomized trials reporting CINV outcomes for the comparison of palonosetron plus 1-day dexamethasone (d1 arm) versus the same regimen followed by dexamethasone on days 2-3 after chemotherapy (d3 arm) in chemotherapy-naive adult patients undergoing either moderately emetogenic chemotherapy (MEC) or anthracycline plus cyclophosphamide (AC)-containing chemotherapy. PubMed and MEDLINE were searched electronically. A manual search was also conducted. The primary endpoint was complete response (CR; no emesis and no rescue medication) in the overall 5-day study period. The noninferiority margin was set at -8.0% (d1 arm-d3 arm).Results Five studies (n = 1,194) were eligible for analysis and all IPD was collected. In the overall study period, the d1 arm showed noninferiority to the d3 arm for CR as well as complete control (pooled risk difference in CR rate - 1.5%, 95% confidence interval [CI] -7.1 to 4.0%, I-2 = 0%; in complete control rate - 2.4%, 95% CI -7.7 to 2.9%, I-2 = 0%). There was no significant interaction between dexamethasone regimen and risk factors (type of chemotherapy, sex, age, and alcohol consumption).Conclusion This IPD meta-analysis indicates that the dexamethasone-sparing regimen is not associated with a significant loss in overall antiemetic control in patients undergoing MEC or AC-containing chemotherapy, irrespective of known risk factors for CINV.Implications for Practice Although dexamethasone in combination with other antiemetic agents has been used to prevent chemotherapy-induced nausea and vomiting (CINV), it is of clinical importance to minimize total dose of dexamethasone in patients undergoing multiple cycles of emetogenic chemotherapy. This individual-patient-data meta-analysis from five randomized controlled trials (1,194 patients) demonstrated a noninferiority of the dexamethasone-sparing regimen for complete response and complete control of CINV. The outcomes were comparable across patients with different characteristics. These findings thus help physicians minimize use of the steroid and further reduce the burden of dexamethasone-related side effects in patients undergoing multiple consecutive courses of emetogenic chemotherapy.