Evaluation of an oral sodium bicarbonate protocol for high-dose methotrexate urine alkalinization.

Rachel D Heisler,Jennifer L Hawker,Janet L Quon,Sara Abedinzadegan Abdi,Josee Z Rioux,Leanne G Fong,Jordan J Kelly,Jennifer C Jupp

doi:10.1007/s00520-021-06503-3

Abstract

Intravenous (IV) sodium bicarbonate is considered standard therapy for high-dose methotrexate (HDMTX) urine alkalinization. Due to a national IV sodium bicarbonate shortage, an oral (PO) sodium bicarbonate protocol was implemented by Alberta Health Services (AHS) for HDMTX urine alkalinization. This study aims to evaluate the efficacy and safety of the PO sodium bicarbonate protocol compared to IV sodium bicarbonate for HDMTX urine alkalinization. A retrospective chart review of adult patients who received HDMTX (>500mg/m2) with sodium bicarbonate for urine alkalinization at 4 hospitals in Alberta was conducted. Patients who received IV sodium bicarbonate between January and June 2017 and PO sodium bicarbonate between July and December 2017 were compared for the primary outcome of time to methotrexate clearance. A total of 84 and 78 HDMTX cycles were included in the IV and PO cohorts, respectively. No difference in time to methotrexate clearance was seen between the IV and PO cohorts, 91.6 (± 35.4) hours and 95.2 (± 44) hours respectively; p = 0.5. The proportion of HDMTX cycles that experienced a > 25% increase in serum creatinine was not statistically significant, IV protocol 12% and PO protocol 5%; p = 0.13. Nausea and emesis occurred more frequently in the PO cohort than the IV cohort, though rarely resulted in refused doses or change to alternate sodium bicarbonate formulations. The results of this study indicate that the AHS PO sodium bicarbonate protocol was no different in time to methotrexate clearance or rates of increased serum creatinine when compared to IV sodium bicarbonate.

Highlights

Methotrexate (MTX) is a folate antimetabolite used at high doses (>500 mg/m2) to treat oncologic diagnoses such as leukemia, lymphoma, and osteosarcoma
At Alberta Health Services (AHS) these supportive care measures are routinely used in all patients receiving high-dose methotrexate (HDMTX)
A total of 177 HDMTX cycles were reviewed for inclusion, of which 15 cycles were excluded for incomplete data (n=6), use of a mixed protocol (n=3), use of an alternate hydration protocol (n=4), administration of sodium acetate (n=1), and errors administering protocol dosing (n=1)

Summary

Introduction

Methotrexate (MTX) is a folate antimetabolite used at high doses (>500 mg/m2) to treat oncologic diagnoses such as leukemia, lymphoma, and osteosarcoma. Along with its therapeutic benefit, high-dose methotrexate (HDMTX) exposure is associated with potentially serious adverse effects. MTX and its metabolites can precipitate in the renal tubules leading to nephrotoxicity in 2-12% of patients [1]. As MTX is primarily renally eliminated, this nephrotoxicity can lead to delayed methotrexate clearance and higher rates of additional adverse effects such as mucositis, myelosuppression, and hepatotoxicity [1, 2]. It is standard practice that patients receiving HDMTX undergo vigorous hydration and urine alkalinization with intravenous (IV) sodium bicarbonate to maintain a urine pH above 7 [1,2,3]. At Alberta Health Services (AHS) these supportive care measures are routinely used in all patients receiving HDMTX

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