Cohen Ian Joseph
The Rina Zaizov Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Cancer Chemother Pharmacol. 2017 Jun;79(6):1057-1065. doi: 10.1007/s00280-017-3304-y. Epub 2017 Apr 28.
To challenge the view that the dose of folinic acid rescue after high-dose methotrexate (MTX) has no significance in the prevention of neurotoxicity and to present the minority view that neurotoxicity can be prevented by an adequate dose of folinic acid, without compromising treatment results. Several fallacies that led to the misunderstanding of post MTX neurotoxicity are presented.
Data mining using search engines was used to find relevant publications, and an e-mail survey of more than 60 authors of articles in this field was performed. All relevant articles identified were read in their entirety.
Examples of clinical studies with neurotoxicity following inadequate rescue are given. Some studies demonstrated no neurotoxicity when adequate doses of folinic acid rescue were started 24-36 h after the start of HDMTX rescue even after mega doses of MTX. Rescue started after 42 h was associated with neurotoxicity except in patients with low serum MTX levels after 24 and 36 h. ALL protocols with neurotoxicity, especially BFM-like protocols, are presented. Protocol is reported in which single protocol changes prevented neurotoxicity.
From the published data, when folinic acid rescue is given in a sufficiently high enough dose and is started 24-36 h after the beginning of the methotrexate exposure, and virtually all forms of post MTX neurotoxicity can be prevented without compromising therapeutic results.
挑战大剂量甲氨蝶呤（MTX）后亚叶酸钙解救剂量对预防神经毒性无意义的观点，并提出少数派观点，即通过足够剂量的亚叶酸钙可预防神经毒性，且不影响治疗效果。文中还阐述了导致对MTX后神经毒性产生误解的几个错误观点。
利用搜索引擎进行数据挖掘以查找相关出版物，并对该领域60多位文章作者进行电子邮件调查。对所有识别出的相关文章进行全文阅读。
给出了挽救不足后出现神经毒性的临床研究实例。一些研究表明，即使在使用超大剂量MTX后，若在HDMTX治疗开始后24 - 36小时开始给予足够剂量的亚叶酸钙解救，则不会出现神经毒性。42小时后开始解救与神经毒性相关，但24小时和36小时后血清MTX水平较低的患者除外。文中展示了所有出现神经毒性的方案，尤其是类似柏林 - 法兰克福 - 明斯特（BFM）方案。报告了一个方案，其中单一方案改变预防了神经毒性。
根据已发表的数据，当在甲氨蝶呤暴露开始后24 - 36小时给予足够高剂量的亚叶酸钙解救时，几乎所有形式的MTX后神经毒性均可预防，且不影响治疗效果。
