<p>A prospective study on urine alkalization with an oral regimen consisting of sodium bicarbonate and acetazolamide in patients receiving high-dose methotrexate</p>

Abstract

Purpose Intravenous (IV) sodium bicarbonate is typically used in alkalization regimens for the safe use of the chemotherapeutic agent high-dose methotrexate (HDMTX). Urine parameters including urine output and pH are important in order to minimize the risk of kidney injury, which increases adverse effects and hospital length of stay following HDMTX. IV sodium bicarbonate has been on shortage, and there are limited literature describing the safety of alternative regimens. Patients and methods A single institution, prospective analysis of non-Hodgkin’s lymphoma and acute lymphoblastic leukemia patients receiving HDMTX for central nervous system (CNS) prophylaxis or disease. Patients received an oral (PO) regimen of sodium bicarbonate and acetazolamide to achieve a urine pH >7. This cohort was compared to a subsequent IV sodium bicarbonate control cohort. Multiple co-primary safety outcomes assessed the incidences of acute kidney injury and delayed methotrexate clearance as well as change in liver function tests. Secondary outcomes included time to urine pH, time to urine output, and length of stay. Results A total of 126 encounters were studied for the primary safety outcome. There was no difference between AKI incidence in patients receiving the PO alkalization regimen compared to patients receiving IV sodium bicarbonate (14.5% vs 9.3%, respectively, P =0.41). There was no difference in methotrexate clearance between the PO and IV groups (26.5% vs 37.2%, respectively, P =0.21). The use of PO alkalization regimen is estimated to have saved 2002 vials of IV sodium bicarbonate and was approximately US$226 less expensive per encounter. Conclusion This analysis supports the use of PO regimens to achieve urine alkalization necessary for safe administration of HDMTX during periods of IV sodium bicarbonate shortage. Further studies may determine optimal dosing strategies that decrease length of stay and ensure noninferiority of efficacy outcomes with PO regimens for urine alkalization with HDMTX.

Comparison of Sodium Bicarbonate and Lactated Ringers Hydration for High-dose Methotrexate Chemotherapy in Children

“…Strategies have included using regularly scheduled enteral sodium bicarbonate, sodium citrate, or acetazolamide in conjunction with IV hydration. 8,[10][11][12][13][14][15] Less commonly, IV sodium acetate was used in place of IV sodium bicarbonate. 7,15 IV fluids, when described, were usually sodium containing fluids, with or without dextrose.…”

“…7,15 IV fluids, when described, were usually sodium containing fluids, with or without dextrose. [12][13][14] Only one cohort described using Lactated Ringers for IV hydration. 8 Similar to our cohort, those that used enteral alkalinization found no difference in time to methotrexate clearance as compared IV sodium bicarbonate.…”

“…8,[10][11][12] Others have also reported no difference in percentage of patients or methotrexate cycles with delayed clearance for enteral alkalinization versus IV sodium bicarbonate. 8,13 Diachinski et al described 29 children receiving highdose methotrexate with either regularly scheduled enteral sodium bicarbonate or sodium citrate with Lactated Ringers (62 cycles) or IV sodium bicarbonate (50 cycles). 8 Similar to our cohort, they found no difference in the percentage of methotrexate cycles that were delayed (8% vs. 10%) or the mean time to methotrexate clearance (57 vs. 61 h).…”

Resource‐appropriate selection of osteosarcoma treatment protocols in low‐ and middle‐income countries

“…Furthermore, there is a lack of pharmacogenomic data on HDMTX metabolism among LMIC patients. Though decreasing the duration of prehydration, oral alkalinization, discharge at higher MTX levels, and standard checklists may reduce the toxicity and supportive care costs, studies from India have established higher treatment costs for HDMTX‐based protocols 6,43–47 . The additional challenge in osteosarcoma is the longer treatment duration of the HDMTX protocols than the non‐HDMTX protocols, leading to significant social and logistic issues in the AYA population 46,48 …”

“…Centers reported 5‐year relapse/progression‐free (PFS) survival rates in patients with osteosarcoma ranging from 40% to 68% with various combinations of the other active drugs (Figure 3A,B; Table 3). 7,8,42–61 The initial proof of non‐HDMTX protocols came from the European Osteosarcoma Intergroup (EOI) trials. While the first EOI trial compared two‐drug protocol Adriamycin‐ cisplatin (AP) to AP with HDMTX, the second trial compared AP to a T10‐like multidrug protocol 48,62 .…”