Dataset Information

Effect of co-medications and potential risk factors of high-dose methotrexate-mediated acute hepatotoxicity in patients with osteosarcoma.

ABSTRACT:

Background

Taiwanese patients frequently experience severe hepatotoxicity associated with high-dose methotrexate (HD-MTX) treatment, which interferes with subsequent treatment. Drug-drug interactions occur when MTX is used in combination with proton pump inhibitors (PPIs), trimethoprim-sulfamethoxazole (TMP-SMX), or non-steroidal anti-inflammatory drugs (NSAIDs). In East Asia, real-world analyses on the effects of co-medication and other potential risk factors on the clinical course of HD-MTX-mediated acute hepatotoxicity in patients with osteogenic sarcoma (OGS) are limited.

Methods

This cohort study included patients with newly diagnosed OGS who were treated with HD-MTX between 2009 and 2017 at Taipei Veterans General Hospital. We collected data on the clinical course of HD-MTX-mediated acute hepatotoxicity, co-medications, and other potential risk factors, and analyzed the effects of these factors on the clinical course of HD-MTX-mediated acute hepatotoxicity.

Results

Almost all patients with OGS treated with HD-MTX developed acute hepatotoxicity with elevated alanine aminotransferase (ALT) levels. Most patients with Grade 3-4 ALT elevation failed to recover to Grade 2 within 7 days. Women and children are high-risk subgroups for HD-MTX-mediated elevation of ALT levels. Age is a factor that contributes to the pharmacokinetic differences of HD-MTX. However, the concurrent use of PPIs, TMP-SMX, or NSAIDs did not affect the elimination of MTX when administered with adequate supportive therapy.

Conclusions

Co-administration of PPIs, TMP-SMX, or NSAIDs may have limited effects on acute hepatotoxicity in well-monitored and adequately pre-medicated patients with OGS undergoing chemotherapy with HD-MTX. Clinicians should pay particular attention to ALT levels when prescribing HD-MTX to children and women.

SUBMITTER: Wang SF

PROVIDER: S-EPMC10278458 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Effect of co-medications and potential risk factors of high-dose methotrexate-mediated acute hepatotoxicity in patients with osteosarcoma.

Wang Sheng-Fan SF Huang Kuan-Wei KW Chou Yueh-Ching YC Lee Hsin-Chen HC Wu Po-Kuei PK Chen Wei-Ming WM Hung Giun-Yi GY Chang Yuh-Lih YL

Cancer medicine 20230416 11

<h4>Background</h4>Taiwanese patients frequently experience severe hepatotoxicity associated with high-dose methotrexate (HD-MTX) treatment, which interferes with subsequent treatment. Drug-drug interactions occur when MTX is used in combination with proton pump inhibitors (PPIs), trimethoprim-sulfamethoxazole (TMP-SMX), or non-steroidal anti-inflammatory drugs (NSAIDs). In East Asia, real-world analyses on the effects of co-medication and other potential risk factors on the clinical course of H ...[more]

PMID: 37062070

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Project description:BackgroundThe role of Methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in the efficacy and toxicity of MTX-based therapy remains uncertain. Our purpose was to clarify whether these two polymorphisms are associated with the outcome of chemotherapy in a cohort of Chinese osteosarcoma (OS) patients treated by high-dose MTX.Methods109 OS patients who had sequentially received high-dose MTX therapy were included in this study. Plasma MTX level was measured routinely at 0, 24, 48 and 72 h after the administration of MTX. Two variants of MTHFR were genotyped using TaqMan SNP Genotyping Assay, including rs1801133 (C667T) and rs1801131 (A1298C). The extent of toxicity induced by MTX, including hematological toxicity, hepatic toxicity, renal toxicity and mucositis, was scored from grade 1 to 4. Severe toxicity was defined as a grade score of ≥3. Patients were dichotomized as follows: grade <3 or ≥3 for toxicity, and ≤0.2 µmol/L or >0.2 µmol/L for plasma MTX level at 72 h. The frequencies of genotypes and allele were compared between the dichotomized groups with the Chi-square test.Results24.8% (27/109) of the patients were found to have significantly high plasma MTX level at the 72 h. Patients with high MTX level at 72 h were found to have significantly higher frequency of genotype TT of rs1801133 (p = 0.002). As for rs1801131, no significant association was found with plasma MTX level. Patients with severe hepatic toxicity or mucositis were found to have remarkably higher incidence of genotype TT of rs1801133 than those with mild toxicity (33.3% vs. 14.8%, p = 0.04 for hepatic toxicity; 34.8% vs. 19.8%, p = 0.05 for mucositis).ConclusionsVariant rs1801133 was confirmed to have remarkable influence on the MTX-induced toxicity. We recommend identification of the genotype of MTHFR variant prior to the application of high-dose MTX to OS patients, which could be an important predictor to screen severe toxicities and thus improve treatment outcomes.

Dataset Information

Effect of co-medications and potential risk factors of high-dose methotrexate-mediated acute hepatotoxicity in patients with osteosarcoma.

Background

Methods

Results

Conclusions

Publications

Effect of co-medications and potential risk factors of high-dose methotrexate-mediated acute hepatotoxicity in patients with osteosarcoma.

Similar Datasets

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