Implementation and evaluation of high-dose methotrexate administration guidelines

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Decreasing Cost and Decreasing Length of Stay After Implementation of Updated High-Dose Methotrexate Discharge Criteria

“…Another study also found similar patterns of low adherence to similar, more stringent monitoring of patients. 14 This practice pattern reflects a comfort level with earlier discharge that has been reinforced in recent clinical trials involving HD-MTX. 15 The patients in our pre-intervention cohort with levels .…”

“…As suggested in previous studies, it may be safe to discharge patients home with an MTX level of 0.1 mmol/L without any supportive medications. 14,15 In our own preintervention cohort, 43% of patients were discharged when their MTX level was . 0.05 mmol/L.…”

“…13 However, the optimal duration for receipt of supportive therapy is somewhat unclear, with several studies suggesting that for patients with normal renal function, leucovorin can be discontinued when the MTX level is # 0.1 mmol/L. 9,14,15 Author affiliations and support information (if applicable) appear at the end of this article.…”

Leucovorin (folinic acid) rescue for high‐dose methotrexate: A review

“…Doses of 500 mg/m 2 or higher are regarded as high‐dose methotrexate (HDMTX) 2,3 . Moreover, HDMTX is the first‐line drug against various malignancies, including lymphomas, acute lymphoblastic leukaemia (ALL), osteosarcoma, and breast cancer 4 …”

“…2,3 Moreover, HDMTX is the first-line drug against various malignancies, including lymphomas, acute lymphoblastic leukaemia (ALL), osteosarcoma, and breast cancer. 4 Although HDMTX is safely administered to the most patients, it can induce serious toxic responses, such as acute kidney injury (2%-12% of patients), gastrointestinal toxicity (10%-30% of patients), liver toxicity (25%-60% of patients), and neurotoxicity (up to 15% of patients). 1,5 Nephrotoxicity is one of the most significant toxicities of MTX.…”