Freeman Karoline, Saunders Mark P, Uthman Olalekan A, Taylor-Phillips Sian, Connock Martin, Court Rachel, Gurung Tara, Sutcliffe Paul, Clarke Aileen
Division of Health Sciences, Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
The Christie, 550 Wilmslow Road, Manchester, M20 4BX, UK.
BMC Cancer. 2016 Jul 25;16:523. doi: 10.1186/s12885-016-2581-x.
Pharmacokinetic guided dosing of 5-fluorouracil chemotherapies to bring plasma 5-fluorouracil into a desired therapeutic range may lead to fewer side effects and better patient outcomes. High performance liquid chromatography and a high throughput nanoparticle immunoassay (My5-FU) have been used in conjunction with treatment algorithms to guide dosing. The objective of this study was to assess accuracy, clinical effectiveness and safety of plasma 5-fluorouracil guided dose regimen(s) versus standard regimens based on body surface area in colorectal cancer.
We undertook a systematic review. MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; EMBASE; Cochrane Library; Science Citation Index and Conference Proceedings (Web of Science); and NIHR Health Technology Assessment Programme were searched from inception to January 2014. We reviewed evidence on accuracy of My5-FU for estimating plasma 5-fluorouracil and on the clinical effectiveness of pharmacokinetic dosing compared to body surface area dosing. Estimates of individual patient data for overall survival and progression-free survival were reconstructed from published studies. Survival and adverse events data were synthesised and examined for consistency across studies.
My5-FU assays were found to be consistent with reference liquid chromatography tandem mass spectrometry. Comparative studies pointed to gains in overall survival and in progression-free survival with pharmacokinetic dosing, and were consistent across multiple studies.
Although our analyses are encouraging, uncertainties remain because evidence is mainly from outmoded 5-fluorouracil regimens; a randomised controlled trial is urgently needed to investigate new dose adjustment methods in modern treatment regimens.
对5-氟尿嘧啶化疗进行药代动力学指导给药，以使血浆5-氟尿嘧啶达到理想的治疗范围，可能会减少副作用并改善患者预后。高效液相色谱法和高通量纳米颗粒免疫测定法（My5-FU）已与治疗算法结合使用以指导给药。本研究的目的是评估在结直肠癌中，基于血浆5-氟尿嘧啶的给药方案与基于体表面积的标准方案相比的准确性、临床有效性和安全性。
我们进行了一项系统评价。检索了MEDLINE、MEDLINE在研及其他未索引引文、EMBASE、Cochrane图书馆、科学引文索引和会议论文集（科学网）以及英国国家卫生研究院卫生技术评估计划，检索时间从起始至2014年1月。我们审查了关于My5-FU估算血浆5-氟尿嘧啶准确性的证据，以及与基于体表面积给药相比药代动力学给药的临床有效性证据。从已发表的研究中重建了个体患者总生存和无进展生存数据的估计值。对生存和不良事件数据进行了综合分析，并检查了各研究之间的一致性。
发现My5-FU测定与参考液相色谱串联质谱法一致。比较研究表明，药代动力学给药可提高总生存率和无进展生存率，且多项研究结果一致。
尽管我们的分析结果令人鼓舞，但仍存在不确定性，因为证据主要来自过时的5-氟尿嘧啶方案；迫切需要进行一项随机对照试验，以研究现代治疗方案中的新剂量调整方法。
