- 學位論文
不同製劑的太平洋紫杉醇副作用之差異-系統性回顧及網路統合分析
The adverse effect of paclitaxel in various formulations - a systematic review and network meta-analysis
摘要
研究目的 本篇網路統合分析使用隨機對照試驗比較太平洋紫杉醇於不同製劑間不良反應差異。包含Solvent-based Paclitaxel（SB-P）、Nanoparticle albumin-bound paclitaxel（Nab-P）、liposomal paclitaxel（Lip-P）、polymeric micelle paclitaxel（PM-P）、polymer-drug conjugates of paclitaxel (PPX) 及polymeric-lipidic nanoparticle paclitaxel (PICN)。 研究方法 系統性搜索資料庫包含Pubmed、Embase、Web of Science、Cochrane、Clinicalkey、Clinicaltrial.com、ASCO及ESMO。將不良反應資料進行分析並計算勝算比及其95%信賴區間並使用CASP Randomised Controlled Trial Checklist評讀文獻。統計分析使用WinBUGS（版本1.4）和NetMetaXL插件工具。 研究結果 包括7011名患者和6種紫杉醇製劑在內的21項研究符合納入標準。於All grade過敏反應部分網路統合分析顯示出相比於SB-P，Lip-P有0.19倍的機率（95% CI= 0.02, 1.3）、Nab-P有0.47倍的機率（95% CI= 0.11, 1.40）、PPX有0.44倍的機率（95% CI= 0.03, 5.7）發生All grade過敏反應。於All grade嗜中性白血球低下症部分網路統合分析顯示相比於Lip-P，SB-P有0.83倍（95% CI= 0.15, 4.81）的機率發生不良反應；相比於PM-P，SB-P有0.73倍（95% CI= 0.22, 2.42）的機率發生不良反應。於三級以上嗜中性白血球低下發燒部分網路統合分析顯示相比於PM-P，SB-P有0.7倍（95% CI= 0.12, 3.56）的機率發生不良反應；相比於PICN，SB-P有0.44倍（95% CI= 0.04, 5.52）的機率發生不良反應。於All grade白血球低下症部分網路統合分析顯示相比於Nab-P，SB-P有0.66倍（95% CI= 0.50, 0.87）的機率發生不良反應；相比於PM-P，SB-P有0.64倍（95% CI= 0.32, 1.16）的機率發生不良反應。周邊感覺神經炎、肌炎與關節炎部分SB-P並無顯著優於也不劣於其他奈米配方。 研究結論 儘管納入文獻提供的不良反應數據有限或不完全，以至研究結果缺乏顯著差異性，但網路統合分析中顯示出奈米粒子的紫杉醇配方其過敏反應發生率傾向低於溶劑型紫杉醇；嗜中性白血球低下症，白血球低下症和嗜中性白血球低下發燒的發生率傾向於高於溶劑型紫杉醇；周邊感覺神經炎、肌炎與關節炎則並不優於也不劣於其他奈米配方。這一結果指出奈米粒子的紫杉醇配方其潛在臨床益處應該與不良反應風險的增加進行權衡。
並列摘要
Background: This network meta-analysis uses randomized controlled trials to compare the adverse effect of paclitaxel in various formulations, including solvent-based paclitaxel (SB-P), nanoparticle albumin-bound paclitaxel (Nab-P), liposomal paclitaxel (Lip-P), polymeric micelle paclitaxel (PM-P), polymer-drug conjugates of paclitaxel (PPX) and polymeric-lipidic nanoparticle paclitaxel (PICN). Methods: Systematically searched PubMed, Embase, Web of Science, Cochrane, Clinicalkey, Clinicaltrial.com, ASCO and ESMO. Data of adverse effect were analyzed to odds ratio (ORs) with 95% confidence interval (CI). The quality of studies was assessed with CASP Randomised Controlled Trial Checklist. Statistical analysis was using WinBUGS software (version 1.4.3) with NetMetaXL interface (version 1.6.1). Results: Twenty-one studies including 7011 patients and 6 paclitaxel formulations fulfilled the inclusion criteria. In all grade hypersensitivity reactions, comparing to SB-P, people with Lip-P had 0.19 times (95% CI= 0.02, 1.3) of chance, with Nab-P had 0.47 times (95% CI= 0.11, 1.40) of chance, with PPX had 0.44 times (95% CI= 0.03, 5.7) of chance for all grade adverse effect. In All grad neutropenia, comparing to Lip-P, people with SB-P had 0.83 times (95% CI= 0.15, 4.81) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.73 times (95% CI= 0.22, 2.42) of chance for all grade adverse effect. In febrile Neutropenia, comparing to PM-P, people with SB-P had 0.7 times (95% CI= 0.12, 3.56) of chance for adverse effect; comparing to PICN, people with SB-P had 0.44 times (95% CI= 0.04, 5.52) of chance for adverse effect. In leucopenia, comparing to Nab-P, people with SB-P had 0.66 times (95% CI= 0.50, 0.87) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.64 times (95% CI= 0.32, 1.16) of chance for all grade adverse effect. The rate of incidence in peripheral sensory neuropathy, myalgias and arthralgias tend to no significant differences between different formulations. Conclusions: Although, the adverse reaction data included in this study were limited or incomplete, and there was no significant difference in the results of this study, this NMA reveal that the nanoparticles paclitaxel formula tends to have a lower incidence of hypersensitivity reactions than solvent-based paclitaxel. Neutropenia, leucopenia, and febrile neutropenia in NMA shows that the rate of incidence with nanoparticles paclitaxel formula tend to higher than solvent-based paclitaxel. The rate of incidence in peripheral sensory neuropathy, myalgias and arthralgias tend to no significant differences between different formulations. This result might point out the potential clinical benefits of nanoparticles paclitaxel formula should be weighed against the increased risk of adverse reactions.