Nowak Thomas J, Lorge Aaron H, Rein Lisa E, Canadeo Angela M, Frank Joel P, Samanas Lisa C, Urmanski Angela M, Atallah Ehab L
Froedtert & The Medical College of Wisconsin, Milwaukee, WI, USA.
J Oncol Pharm Pract. 2019 Oct;25(7):1675-1681. doi: 10.1177/1078155218808866. Epub 2018 Oct 25.
High-dose methotrexate is used to treat a variety of malignancies. Methotrexate-associated supportive care and the threshold methotrexate level for the discontinuation of supportive care are not consistent among studies. We evaluated the implementation of high-dose methotrexate administration guidelines, which raised the standard threshold methotrexate level for the discontinuation of supportive care from <0.05 to <0.1 µmol.
A single-center, observational analysis of patients receiving high-dose methotrexate from 1 January 2015 to 31 May 2017 was conducted. The primary endpoint was time from the start of the methotrexate infusion until the discontinuation of the sodium bicarbonate infusion, before and after guideline implementation.
Fifty-two patients met the inclusion criteria, which comprised of a total of 136 individual methotrexate doses and were included in the retrospective analysis. Twenty-four patients were included in the prospective analysis, which comprised a total of 46 individual methotrexate doses. The primary endpoint, time until discontinuation of the sodium bicarbonate infusion, was a median of 97.7 h in the retrospective group versus 73.2 h in the prospective group (p = 0.098). Secondary endpoints also favored patients in the prospective group, including hours of hospitalization, number of methotrexate levels checked, weight gained during admission, and adherence to the guideline.
Among patients who received high-dose methotrexate, implementation of a guideline using a methotrexate threshold of <0.1 µmol was able to significantly decrease the time to discontinuation of supportive care and subsequently may lead to early hospital discharge given that we did not show a statistical significance.
高剂量甲氨蝶呤用于治疗多种恶性肿瘤。甲氨蝶呤相关的支持治疗以及停止支持治疗的甲氨蝶呤阈值在各研究中并不一致。我们评估了高剂量甲氨蝶呤给药指南的实施情况,该指南将停止支持治疗的标准甲氨蝶呤阈值从<0.05 μmol提高到了<0.1 μmol。
对2015年1月1日至2017年5月31日接受高剂量甲氨蝶呤治疗的患者进行单中心观察性分析。主要终点是在指南实施前后,从甲氨蝶呤输注开始至碳酸氢钠输注停止的时间。
52例患者符合纳入标准,共包括136次甲氨蝶呤单剂量给药,并纳入回顾性分析。24例患者纳入前瞻性分析,共包括46次甲氨蝶呤单剂量给药。主要终点,即碳酸氢钠输注停止时间,回顾性组中位数为97.7小时,前瞻性组为73.2小时(p = 0.098)。次要终点也有利于前瞻性组的患者,包括住院时间、甲氨蝶呤水平检查次数、入院期间体重增加以及对指南的依从性。
在接受高剂量甲氨蝶呤治疗的患者中,实施甲氨蝶呤阈值<0.1 μmol的指南能够显著缩短停止支持治疗的时间,鉴于我们未显示出统计学意义,随后可能导致早期出院。