Effect of proton pump inhibitors on high-dose methotrexate elimination: a systematic review and meta-analysis

2020 ◽  
Vol 42 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Xi Wang ◽  
Yanqin Song ◽  
Jingjing Wang ◽  
Jin He ◽  
Ruming Liu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Meta Analysis ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Cranial Irradiation for Pediatric T-Lineage Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2580-2580
Author(s):  
Michael J. Kelly ◽  
Thomas A. Trikalinos ◽  
D. Matthew Gianferante ◽  
Susan K. Parsons
Keyword(s):  
Systematic Review ◽  
Lymphoblastic Leukemia ◽  
Meta Analysis ◽  
Cranial Irradiation ◽  
Intrathecal Chemotherapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Event Free Survival ◽  
Free Survival ◽  
Dose Methotrexate

Abstract Abstract 2580 Background There is currently a heterogeneous approach to the use of cranial irradiation (CRT) for central nervous system (CNS) directed therapy for T-lineage acute lymphoblastic leukemia (T-ALL) by pediatric cooperative groups. We sought to explore the association of CRT and event-free survival (EFS) in children with T-ALL by means of a systematic review and meta-analysis. Methods We searched MEDLINE from 1949 to 2012 without geographic restrictions, to identify English language randomized trials or cohort studies reporting EFS in children with T-ALL who received CNS directed therapy. For studies to be eligible a CRT strategy needed to be described (intrathecal chemotherapy +/− cranial irradiation) and at least 3-year EFS (or longer) needed to be reported. Studies need to include at least 10 pediatric subjects with T-ALL; there was not a minimum proportion of T-ALL subjects needed to meet eligibility criteria. The following study characteristics were extracted for each study: eligibility criteria, patient number, CRT strategy, intrathecal chemotherapy administered and number of doses, steroid administered in induction, cumulative doses of high-dose methotrexate, asparaginase, and anthracyclines, definition of event-free survival, median follow-up, and event-free survival. We conducted subgroup analyses (random effects) and random effects meta-regressions to explore associations between EFS and the following study-level factors: (i) CRT strategy, categorized as cranial irradiation for all subjects, cranial irradiation administered in a risk-directed fashion (often stratified by age and WBC count at diagnosis), cranial irradiation for CNS positive patients only, and omission of CRT for all patients; (ii) enrollment year (continuous); (iii) intrathecal chemotherapy (methotrexate vs. triple intrathecal chemotherapy); (iv) maximum number of intrathecal chemotherapy dose (<10 vs. 10–19 vs. > 20); (v) high-dose methotrexate (dose > 1 gram/m2) present or absent; (vi) high cumulative dose of asparaginase (> 400,000 IU/m2) present or absent, (vii) high cumulative dose of anthracyclines (doxorubicin plus daunorubicin total > 300 mg/m2)present or absent; (viii) induction steroid (prednisone vs. dexamethasone). Results The search returned 2383 abstracts, 491 of which were reviewed in full text. Eligible were 59 articles (5726 T-ALL patients enrolled between 1973 and 2005). The overall 3-year EFS was 62.1% (95% CI: 58.9% to 65.3%). There was significant heterogeneity among the treatment studies (I2̂ = 80%, p < 0.001). An improvement in EFS was significantly associated with the year study enrollment began (p< 0.001); based on a meta-regression model of EFS versus year of enrollment start, the average EFS improved from 44% for studies that began in 1980 to 71% for studies that began in 2000. The EFS was significantly different across the 4 CRT categories (omnibus p-value=0.02): CRT to all patients (EFS: 63%, 95% CI: 58% to 67%) risk-directed CRT (EFS: 59%, 95% CI: 53% to 65%), CRT for CNS positive patients only (EFS: 55%, 95% CI: 41% to 68%), CRT omitted for all patients (EFS: 74%, 95% CI: 67% to 80%). The association of EFS and CRT strategies remained in the same direction after adjusting for year of enrollment. The following factors were also associated with an increased odds of EFS on univariate analysis: the administration of 10–19 or > 20 doses of intrathecal chemotherapy (OR: 1.84, 95% CI: 1.32 to 2.58 and OR: 1.95, 95% CI: 1.31 to 2.94, respectively), the administration of high dose methotrexate (OR: 1.43, 95% CI: 1.06 to 1.93), and the administration of more than 400,000 IU/m2 of asparaginase (OR: 1.79, 95% CI: 1.27 to 2.51). However after adjusting for the year of enrollment, only high doses of asparaginase remained significantly associated with EFS. Conclusion Our systematic review and meta-analysis found that CRT strategy is associated with EFS for children with T-ALL. Studies that omitted CRT were associated with superior EFS; however, these studies were more recent, and there was an improvement in EFS with time. The administration of more than 400,000 IU/m2 of asparaginase was also associated with lower relapse rates. Although these noncausal associations are congruent with the notion that CRT may not offer an improvement in survival for children with T-ALL given current chemotherapeutic options, the existing evidence-based is not sufficient to draw such a conclusion. Disclosures: Off Label Use: asparaginase is a a drug used to treat acute lymphoblastic leukemia.

scholarly journals Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia

2020 ◽  
Vol 32 (5) ◽  
pp. 292-299 ◽  
Author(s):  
Phung Anh Nguyen ◽  
Mohaimenul Islam ◽  
Cooper J Galvin ◽  
Chih-Cheng Chang ◽  
Soo Yeon An ◽  
...  
Keyword(s):  
Systematic Review ◽  
Random Effects ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Observational Studies ◽  
Meta Analysis ◽  
Community Acquired Pneumonia ◽  
Cochrane Library ◽  
High Dose ◽  
Increased Risk

Abstract Purpose Proton pump inhibitors (PPIs), one of the most widely used medications, are commonly used to suppress several acid-related upper gastrointestinal disorders. Acid-suppressing medication use could be associated with increased risk of community-acquired pneumonia (CAP), although the results of clinical studies have been conflicting. Data sources A comprehensive search of MEDLINE, EMBASE and Cochrane library and Database of Systematic Reviews from the earliest available online year of indexing up to October 2018. Study selection We performed a systematic review and meta-analysis of observational studies to evaluate the risk of PPI use on CAP outcomes. Data extraction Included study location, design, population, the prevalence of CAP, comparison group and other confounders. We calculated pooled odds ratio (OR) using a random-effects meta-analysis. Results of data synthesis Of the 2577 studies screening, 11 papers were included in the systematic review and 7 studies with 65 590 CAP cases were included in the random-effects meta-analysis. In current PPI users, pooled OR for CAP was 1.86 (95% confidence interval (CI), 1.30–2.66), and in the case of recent users, OR for CAP was 1.66 (95% CI, 1.22–2.25). In the subgroup analysis of CAP, significance association is also observed in both high-dose and low-dose PPI therapy. When stratified by duration of exposure, 3–6 months PPIs users group was associated with increased risk of developing CAP (OR, 2.05; 95% CI, 1.22–3.45). There was a statistically significant association between the PPI users and the rate of hospitalization (OR, 2.59; 95% CI, 1.83–3.66). Conclusion We found possible evidence linking PPI use to an increased risk of CAP. More randomized controlled studies are warranted to clarify an understanding of the association between PPI use and risk of CAP because observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding.

scholarly journals Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy

2009 ◽  
Vol 67 (1) ◽  
pp. 44-49 ◽  
Author(s):  
Kunihiro Suzuki ◽  
Kosuke Doki ◽  
Masato Homma ◽  
Hirofumi Tamaki ◽  
Satoko Hori ◽  
...  
Keyword(s):  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Methotrexate Therapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Tu1820 The Impact of Co-Administration of Proton Pump Inhibitors on Plasma Methotrexate Clearance in High-Dose Methotrexate Therapy

2013 ◽  
Vol 144 (5) ◽  
pp. S-854-S-855 ◽  
Author(s):  
Koh Imbe ◽  
Naoyoshi Nagata ◽  
Chizu Yokoi ◽  
Kazuhiro Watanabe ◽  
Etsuko Yokota ◽  
...  
Keyword(s):  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Methotrexate Therapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
The Impact

scholarly journals The Role of Genetic Polymorphisms in High-Dose Methotrexate Toxicity and Response in Hematological Malignancies: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zaiwei Song ◽  
Yang Hu ◽  
Shuang Liu ◽  
Dan Jiang ◽  
Zhanmiao Yi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Genetic Association ◽  
Hematological Malignancies ◽  
Renal Toxicity ◽  
Meta Analysis ◽  
High Dose ◽  
Cochrane Central Register ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Objective: High-dose methotrexate (HDMTX) is a mainstay therapeutic agent for the treatment of diverse hematological malignancies, and it plays a significant role in interindividual variability regarding the pharmacokinetics and toxicity. The genetic association of HDMTX has been widely investigated, but the conflicting results have complicated the clinical utility. Therefore, this systematic review aims to determine the role of gene variants within the HDMTX pathway and to fill the gap between knowledge and clinical practice.Methods: Databases including EMBASE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and the Clinical Trials.gov were searched from inception to November 2020. We included twelve single-nucleotide polymorphisms (SNPs) within the HDMTX pathway, involving RFC1, SLCO1B1, ABCB1, FPGS, GGH, MTHFR, DHFR, TYMS, and ATIC. Meta-analysis was conducted by using Cochrane Collaboration Review Manager software 5.3. The odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (95% CI) were analyzed to evaluate the associations between SNPs and clinical outcomes. This study was performed according to the PRISMA guideline.Results: In total, 34 studies with 4102 subjects were identified for the association analysis. Nine SNPs involving MTHFR, RFC1, ABCB1, SLCO1B1, TYMS, FPGS, and ATIC genes were investigated, while none of studies reported the polymorphisms of GGH and DHFR yet. Two SNPs were statistically associated with the increased risk of HDMTX toxicity: MTHFR 677C&gt;T and hepatotoxicity (dominant, OR=1.52, 95% CI=1.03-2.23; recessive, OR=1.68, 95% CI=1.10–2.55; allelic, OR=1.41, 95% CI=1.01–1.97), mucositis (dominant, OR=2.11, 95% CI=1.31–3.41; allelic, OR=1.91, 95% CI=1.28–2.85), and renal toxicity (recessive, OR=3.54, 95% CI=1.81–6.90; allelic, OR=1.89, 95% CI=1.18–3.02); ABCB1 3435C&gt;T and hepatotoxicity (dominant, OR=3.80, 95% CI=1.68-8.61), whereas a tendency toward the decreased risk of HDMTX toxicity was present in three SNPs: TYMS 2R&gt;3R and mucositis (dominant, OR=0.66, 95% CI=0.47–0.94); RFC1 80A&gt;G and hepatotoxicity (recessive, OR=0.35, 95% CI=0.16–0.76); and MTHFR 1298A&gt;C and renal toxicity (allelic, OR=0.41, 95% CI=0.18–0.97). Since the data of prognosis outcomes was substantially lacking, current studies were underpowered to investigate the genetic association.Conclusions: We conclude that genotyping of MTHFR and/or ABCB1 polymorphisms prior to treatment, MTHFR 677C&gt;T particularly, is likely to be potentially useful with the aim of tailoring HDMTX therapy and thus reducing toxicity in patients with hematological malignancies.

scholarly journals High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junyao Yu ◽  
Huaping Du ◽  
Xueshi Ye ◽  
Lifei Zhang ◽  
Haowen Xiao
Keyword(s):  
Meta Analysis ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Dose Methotrexate

AbstractWith the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL). This review focused on first-line induction and consolidation treatment of PCNSL and aimed to determine the optimal combination of HD-MTX and the long-term beneficial consolidation methods. A comprehensive literature search of MEDLINE identified 1407 studies, among which 31 studies met the inclusion criteria. The meta-analysis was performed by using Stata SE version 15. Forest plots were generated to report combined outcomes like the complete response rate (CRR), overall survival, and progression-free survival. We also conducted univariate regression analyses of the baseline characteristics to identify the source of heterogeneity. Pooled analysis showed a CRR of 41% across all HD-MTX-based regimens, and three- and four-drug regimens had better CRRs than HD-MTX monotherapy. In all combinations based on HD-MTX, the HD-MTX + procarbazine + vincristine (MPV) regimen showed pooled CRRs of 63% and 58% with and without rituximab, respectively, followed by the rituximab + HD-MTX + temozolomide regimen, which showed a pooled CRR of 60%. Pooled PFS and OS showed that post-remission consolidation with autologous stem cell transplantation (ASCT) was associated with the best survival outcome, with a pooled 2-year OS of 80%, a 2-year PFS of 74%, a 5-year OS of 77%, and a 5-year PFS of 63%. Next, whole-brain radiation therapy (WBRT) + chemotherapy showed a pooled 2-year OS of 72%, 2-year PFS of 56%, 5-year OS of 55%, and 5-year PFS of 41%, with no detectable CR heterogeneity throughout the entire treatment process. In HD-MTX-based therapy of newly diagnosed PCNSL, MPV with or without rituximab can be chosen as the inductive regimen, and the rituximab + HD-MTX + temozolomide regimen is also a practical choice. Based on our study, high-dose chemotherapy supported by ASCT is an efficacious approach for consolidation. Consolidation with WBRT + chemotherapy can be another feasible approach.

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