Evaluation of methotrexate clearance with an enteral urine alkalinization protocol for patients receiving high-dose methotrexate

Abstract

Purpose

High-dose methotrexate is a cytotoxic agent used to treat several malignancies. Urine alkalinization with sodium bicarbonate and hyperhydration are given with methotrexate to prevent drug precipitation in the kidneys. Due to a nationwide intravenous sodium bicarbonate shortage, an enteral-based urine alkalinization protocol was instituted. This study compared outcomes and adverse effects between the previously used intravenous and newly implemented enteral protocols.

Methods

Single center retrospective cohort study comparing parenteral and enteral urine alkalinization for patients that received methotrexate doses ≥ 500 mg/m² between 1 April 2016 and 1 October 2018. The primary endpoint was time to methotrexate clearance. Secondary outcomes included length of stay, time to administration of methotrexate, amount of sodium bicarbonate utilized, toxicities of methotrexate, and protocol-associated adverse effects.

Results

There were 67 patients included in the study for a total of 195 infusions. The average time to methotrexate clearance between the two cohorts was similar (parenteral 88 h vs. enteral 98 h p = 0.06). Likewise, length of stay was not different between the two cohorts (p = ns). The enteral cohort methotrexate’s doses were initiated faster and received significantly less intravenous sodium bicarbonate when compared to the parenteral cohort (p = 0.04). Rates of acute kidney injury, neutropenia, hepatotoxicity, and mucositis were similar between the two groups. There were higher rates of diarrhea and low serum bicarbonate values in the enteral cohort.

Conclusion

This study supports the ability to conserve intravenous sodium bicarbonate by using an enteral-based urine alkalization regimen for HD methotrexate, with no difference in outcomes or toxicity.