scholarly journals Oral Regimen for Urine Alkalization in Patients Receiving High Dose Methotrexate during a National Shortage of Intravenous Sodium Bicarbonate

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2309-2309 ◽  
Author(s):  
Daniel R Reed ◽  
Jeremy M Sen ◽  
Eric J Pierce ◽  
Maria C Nicolais ◽  
Michael K Keng
Keyword(s):  
Length Of Stay ◽  
Sodium Bicarbonate ◽  
Categorical Variables ◽  
Published Data ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Start Time ◽  
Urine Ph ◽  
Dose Methotrexate ◽  
The Impact

Abstract Background: High dose methotrexate (MTX) is an important agent in the prevention and treatment of cancer in the central nervous system. Administration of this drug requires alkalization of the urine, which traditionally includes the use of intravenous (IV) sodium bicarbonate (bicarb). In May 2017, IV bicarb was on national shortage; at the University of Virginia, pharmacists and physicians designed an oral (PO) regimen using bicarb and acetazolamide to ensure patients could continue receiving MTX. As there are limited published data, we aimed to assess the safety and the impact on time to start of MTX. Methods: Retrospective chart review was done 5/2016-4/2017 to establish a baseline time to methotrexate. In a prospective analysis, data was collected from May 2017 to May 2018 on all patients who received MTX. For patients receiving the PO regimen, bicarb 2,600 mg PO 6 times daily and acetazolamide 250 mg PO every 6 hours were the initial doses and titrated to maintain a urine pH greater than or equal to 7. The primary endpoint was time to MTX for patients with planned admissions who start MTX upon meeting urine pH and output parameters. Secondary endpoints included incidence of acute kidney injury (AKI) and delayed methotrexate clearance for all patient encounters. AKI was defined using Kidney Disease Improving Global Outcomes criteria. Delayed MTX clearance was defined based on failure to meet goal levels based on published chemotherapy protocols. χ2 analysis was completed on categorical variables. A statistical process control chart (p-chart) depicted time to MTX. Results: A total of 162 patient encounters were included in the analysis. The median age of patients receiving oral bicarb was 51 years (range 21-69) and was 51 years (range 21-63) for patients receiving IV bicarb. Eighty-six encounters were planned admissions that started MTX when urine parameters were met and received either IV (n=32) or PO bicarb (n=54). In these patients median time from admission to MTX was 8.4 vs 7.9 hours, respectively. Figure 1 shows consecutive patients receiving MTX prior to, during, and after resolution of the IV bicarb shortage; there is less variability and fewer outliers in the MTX start time when exclusively administering the PO regimen during the shortage. For the secondary analysis an additional 76 encounters with either unplanned admissions or predetermined MTX start time on subsequent day to admission were analyzed for safety outcomes. The rate of AKI was 14.5% vs 8.9% in the PO vs IV groups, respectively (p=0.28). There was no difference in incidence of delayed methotrexate clearance with 26.5% of patients in PO group vs 25.3% patients in IV group (p=0.87). Length of stay was slightly increased in patients who received PO vs IV alkalization (3.78 vs 3.15 days). Conclusion: Our alternative oral bicarb and acetazolamide urine alkalization regimen appears safe in patients receiving MTX and allowed for continued treatment of patients during a national IV bicarb shortage. Time to start of MTX was decreased with implementation of PO regimen, and there appeared to be a more predictable start time for MTX. While not significant, the higher incidence of AKI in PO group warrants further analysis. Future efforts include using oral outpatient alkalization prior to inpatient admission to work towards improving length of stay. Disclosures No relevant conflicts of interest to declare.

A single-center qualitative study evaluating the safety and efficacy of a pharmacist-driven protocol for high-dose methotrexate management

2020 ◽  
pp. 107815522092745
Author(s):  
Stephanie F Matta ◽  
Leslie A Gieselman ◽  
Robert S Mancini
Keyword(s):  
Length Of Stay ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Improvement Project ◽  
Treatment Delays ◽  
Dose Methotrexate ◽  
Significant Difference ◽  
The Impact ◽  
Inpatient Length Of Stay

Introduction Delayed methotrexate clearance in several patients admitted to the oncology unit at a regional medical center necessitated the development of a pharmacist-driven protocol for supportive therapy with high-dose methotrexate. This performance improvement project evaluated the impact of the protocol on inpatient length of stay, patient safety, and clinical outcomes. Methods Retrospective data were collected over 14 months pre-implementation and prospective data were collected over 19 months post-implementation. Primary outcomes included mean length of stay and incidence of kidney injury. Secondary outcomes included myelosuppression, treatment delays, mucositis, protocol adherence, and pharmacist interventions. Chi-squared and unpaired two sample t-test were used for data analysis. Intervention A literature review of consensus recommendations for supportive care post high-dose methotrexate administration was conducted to develop the protocol. Education on implementation was provided to involved disciplines. Results One-hundred ten high-dose methotrexate admissions for 23 patients were analyzed: 24 pre-protocol and 86 post-protocol. Mean length of stay was 5.17 nights pre-protocol and 3.91 nights post-protocol ( p = 0.026). Incidence of kidney injury significantly decreased (16.7% pre-protocol versus 3.5% post-protocol; p = 0.0394). Lower incidences of all-grade anemia (83.3% versus 58.1%), neutropenia (62.5% versus 29.1%), and thrombocytopenia (58.3% versus 33.7%) as well as treatment delays (29.2% versus 11.6%; p = 0.036) were reported post protocol. No statistically significant difference in mucositis was detected. Pharmacist adherence to protocol was ≥80% resulting in 348 interventions with 99.4% provider acceptance. Conclusion The implementation of a pharmacist-driven high-dose methotrexate management protocol resulted in a statistically significant decrease in inpatient length of stay and kidney injury. Further studies are needed to assess the impact on additional outcomes.

scholarly journals Safety and Effectiveness of a Pharmacist-Driven High-Dose Methotrexate Monitoring Protocol at an Academic Medical Center

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4572-4572
Author(s):  
Kendra Jones ◽  
Leila Mohassel ◽  
Raymund Cuevo
Keyword(s):  
Length Of Stay ◽  
Supportive Care ◽  
Drug Interactions ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Urine Ph ◽  
Protocol Implementation ◽  
Monitoring Protocol ◽  
Protocol Group ◽  
Dose Methotrexate

Abstract Introduction: High-dose methotrexate (HD-MTX) requires extensive monitoring and implementation of supportive care strategies to prevent associated toxicities. Although monitoring protocols for MTX vary across institutions, standardized supportive care measures can improve treatment outcomes. The purpose of this study was to evaluate the impact of a pharmacist-driven monitoring protocol on management of patients with delayed MTX elimination. Methods: This was a single-center, retrospective analysis that included hospitalized adult cancer patients receiving HD-MTX therapy (≥ 1 g/m 2). The study consisted of a pre-protocol group (August 2014 to July 2017) and a post-protocol group (August 2017 to August 2020). Patients were included in the analysis more than once if they had a repeat but separate hospital encounter. The primary outcome measure was to compare the rate of appropriate leucovorin dosage adjustments, defined by adherence to institution-specific HD-MTX monitoring guidelines, before and after protocol implementation (Table 1). Secondary outcomes included MTX concentrations at 24, 48, and 72 hours; time to MTX elimination; evidence of delayed MTX clearance; urine pH; length of stay; drug-drug interactions; and incidence of toxicities. Group comparisons for continuous data were made using Mann-Whitney U test and Chi-square or Fisher's exact test was used for categorical data. A p-value of < 0.05 was used to indicate significance. Results: Of 272 hospital encounters initially identified, 82 pre-protocol encounters and 59 post-protocol encounters were included in the analysis. Thirty-five percent of patient encounters in the pre-protocol group were excluded as a result of inappropriately timed methotrexate levels compared to only 9% in the post-protocol group, indicating improved MTX monitoring after protocol implementation. Baseline characteristics are summarized in Table 2. The most common malignancy was primary CNS lymphoma (53.8%) followed by non-Hodgkin lymphoma (28.8%). HD-MTX monotherapy was the most common regimen used in the pre-protocol group (57.1%) whereas combination therapy with rituximab +/- procarbazine was the most common regimen used in the post-protocol group (62.5%). Twenty-one encounters in the pre-protocol group and 22 encounters in the post-protocol group required leucovorin dose escalations at 24, 48, or 72 hours (Table 3). Following the implementation of the pharmacist-driven protocol, the rate of appropriate leucovorin dose adjustments increased significantly from 61.9% to 90.9% (p = 0.034). The median methotrexate concentration at 48 and 72 hours was higher in the post-protocol group when compared to the pre-protocol group. [0.22 µM/L vs.0.18 µM/L (p = 0.019) and 0.1 µM/L vs. 0.07 µM/L (p < 0.001), respectively]. Median time to methotrexate elimination was slightly longer in patients managed according to the MTX protocol [73 hours vs. 72.4 hours, p = 0.022] with higher rates of delayed clearance noted in these patients [18 (30.5%) vs. 16 (19.5%), p < 0.001]. There were no statistically significant differences in length of stay, urine pH, or drug-drug interactions between the two groups during methotrexate therapy (Table 4). However, a lower percentage of concomitant drug interactions with methotrexate were identified after protocol implementation, suggesting improved drug interaction screening [29 (49.2%) vs. 53 (64.9%), p = 0.857]. Rates of toxicities are shown in Table 5. The post-protocol group experienced a higher incidence of any-grade hyperbilirubinemia [20 (33.9%) vs. 18 (22%), p = 0.019], encephalopathy [10 (17%) vs. 5 (6.1%), p = 0.043], and grade ≥ 3 neutropenia [4 (6.8%) vs. 4 (4.9%), p = 0.009]. These differences in toxicity rates may in part be due to more frequent use of multi-agent chemotherapy in the post-protocol group and greater number of MTX cycles administered to these patients. The incidence of nephrotoxicity was similar in both groups (6 (7.3%) vs. 5 (8.5%), p= 0.493) and in line with previous reports. Conclusion:The implementation of a pharmacist-driven HD-MTX monitoring protocol improved optimal timing of MTX serum concentrations, resulted in a statistically significant improvement in the rate of appropriate leucovorin dose escalations, and led to enhanced detection of drug interactions. These findings demonstrate the important role pharmacists can play in dosing and monitoring high-risk regimens. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Safety and efficacy of a urine alkalinization protocol developed for high-dose methotrexate patients during intravenous bicarbonate shortage

2019 ◽  
Vol 25 (8) ◽  
pp. 1860-1866 ◽  
Author(s):  
Amanda M Roy ◽  
Matthew Lei ◽  
Uvette Lou
Keyword(s):  
Sodium Bicarbonate ◽  
Creatinine Clearance ◽  
Urine Output ◽  
Retrospective Chart Review ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Urine Ph ◽  
Dose Methotrexate ◽  
Mean Time ◽  
Intravenous Sodium

Purpose Urinary alkalinization with intravenous sodium bicarbonate is standard during high-dose methotrexate administration. Due to a national intravenous sodium bicarbonate shortage, a urinary alkalinization protocol involving hyperhydration with intravenous fluids, oral bicarbonate, and intravenous or oral acetazolamide was utilized from 10 April to 30 May 2017 (“shortage protocol”). This study compared outcomes between protocols. Methods A single-center, retrospective chart review was conducted for adults who received methotrexate ≥500 mg/m2 on ≥ two occasions, at least once during each protocol, between 19 February and 19 July 2017. Results Eighteen patients (50% male), median age 65 years, received 76 total high-dose methotrexate cycles. Shortage protocol was used in 37 cycles (48.7%). Mean time to methotrexate clearance did not differ between groups (p = ns). Mean time to urinary alkalinization and duration of hospitalization were not statistically different (p = 0.49 and 0.23, respectively). Average total bicarbonate administered per 24 hours was higher in standard protocol (p < 0.05), but hydration rates were similar (p = 0.73). Creatinine clearance and urine output on days 1 and 2 post-high-dose methotrexate did not significantly differ (creatinine clearance day 1, p = 0.27; creatinine clearance day 2, p = 0.55; urine output day 1, p = 0.62; urine output day 2, p = 0.60). Interruptions in alkalinization were significantly higher during shortage (0.41 ± 0.75 instances of urine pH < 7 during standard vs. 1.3 ± 1.7 under shortage, p < 0.05).

scholarly journals Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2945
Author(s):  
Mélanie Mercier ◽  
Corentin Orvain ◽  
Laurianne Drieu La Rochelle ◽  
Tony Marchand ◽  
Christopher Nunes Gomes ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Skeletal Involvement ◽  
Large B Cell Lymphoma ◽  
Dose Methotrexate ◽  
The Impact ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up. Fifty patients (54%) received upfront HD-MTX for prophylaxis of CNS recurrence (high IPI score and/or epidural involvement) or because of skeletal involvement. After adjusting for age, ECOG, high LDH levels, and type of skeletal involvement, HD-MTX was associated with an improved PFS and OS (HR: 0.2, 95% CI: 0.1–0.3, p < 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p < 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p <0.001 and 83 vs. 58%, p < 0.001). Radiotherapy was associated with an improved 5-year PFS (74 vs. 48%, p = 0.02), whereas 5-year OS was not significantly different (79% vs. 66%, p = 0.09). A landmark analysis showed that autologous stem cell transplantation was not associated with improved PFS or OS. The combination of high-dose methotrexate and an anthracycline-based immunochemotherapy is associated with an improved outcome in patients with DLBCL and skeletal involvement and should be confirmed in prospective trials.

Early Hydration and Alkalinization-Decreased Length of Stay for High-Dose Methotrexate (HDMTX

2002 ◽  
Vol 19 (2) ◽  
pp. 55-55
Author(s):  
Teresa J. Robinson ◽  
Linda Wells ◽  
Teresa Braziel ◽  
Emily Thomas ◽  
D. Luke Holland ◽  
...  
Keyword(s):  
Length Of Stay ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Early Hydration ◽  
Dose Methotrexate

Combined treatment with high-dose methotrexate and whole brain radiation improves survival in primary central nervous system lymphoma (PCNSL)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18520-18520
Author(s):  
M. A. Abdelsalam ◽  
G. Hussainy ◽  
S. Akhtar ◽  
I. Maghfoor ◽  
A. Elweshi ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prognostic Factors ◽  
Combined Treatment ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Phase Ii Trials ◽  
Whole Brain ◽  
Cox Regression Analysis ◽  
Dose Methotrexate ◽  
The Impact

18520 Background: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor, cranial irradiation alone rarely result in long term disease control or prolonged survival. We analyzed our data for the impact of adding high dose methotrexate (HDMTX) prior to whole brain irradiation (WBI). Methods: All patients with PCNSL diagnosed and managed during 1991–2004 were identified from Oncology Data Unit. Patient’s characteristics, prognostic factors, details of treatment and outcome were reviewed. Sixty-two patients were identified, 10 were excluded (4 had WBI < 40 Gy and 6 had no treatment). Radiation alone was considered curative with a dose ≥ 40 Gy. Combined modality therapy included 3–4 cycles of HDMTX (3gm/m2) followed by WBI Results: 52 patients were analyzed for outcome. 36 had WBI, dose ≥40 Gy, 16 received 3–4 cycle of HDMTX followed by WBI (chemo-radiotherapy (CRT)). Median age was 48.2 years; 42 years in CRT group, 51 years in WBI. Patients characteristics were comparable between two groups except for higher multifocal tumor in CRT group (92% vs. x22%, p=0.029). Median follow is 12.83±6.4 months. Results are shown in Table . HR for event is 0.64 (95% CI was 0.52–0.98) and for death 0.58 (95% CI was 0.48–0.92), both in favor of CRT. Univariate regression analysis using one-way analyses of variance (ANOVA) and multivariate Cox regression analysis for prognostic factors including age (< 60 vs. ≥60), ECOG PS (0–2 vs. 3–4), extent of surgery (biopsy vs. debulking), solitary vs mutifocal tumor and dose of radiation therapy (< 50Gy vs. ≥50Gy) failed to identify any prognostic factor. Conclusions: This retrospective comparison supports other phase II trials results that high dose methotrexate followed by WBI in PCNSL improves outcome. [Table: see text] No significant financial relationships to disclose.

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

2021 ◽  
Author(s):  
Rachel D. Heisler ◽  
Jordan J. Kelly ◽  
Sara Abedinzadegan Abdi ◽  
Jennifer L. Hawker ◽  
Leanne G. Fong ◽  
...  
Keyword(s):  
Sodium Bicarbonate ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Urine Alkalinization ◽  
Oral Sodium
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