{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T17:41:40Z","timestamp":1769276500902,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,4,16]],"date-time":"2023-04-16T00:00:00Z","timestamp":1681603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"publisher","award":["V112C\u2010047"],"award-info":[{"award-number":["V112C\u2010047"]}],"id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Taiwanese patients frequently experience severe hepatotoxicity associated with high\u2010dose methotrexate (HD\u2010MTX) treatment, which interferes with subsequent treatment. Drug\u2013drug interactions occur when MTX is used in combination with proton pump inhibitors (PPIs), trimethoprim\u2010sulfamethoxazole (TMP\u2010SMX), or non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs). In East Asia, real\u2010world analyses on the effects of co\u2010medication and other potential risk factors on the clinical course of HD\u2010MTX\u2010mediated acute hepatotoxicity in patients with osteogenic sarcoma (OGS) are limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This cohort study included patients with newly diagnosed OGS who were treated with HD\u2010MTX between 2009 and 2017 at Taipei Veterans General Hospital. We collected data on the clinical course of HD\u2010MTX\u2010mediated acute hepatotoxicity, co\u2010medications, and other potential risk factors, and analyzed the effects of these factors on the clinical course of HD\u2010MTX\u2010mediated acute hepatotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Almost all patients with OGS treated with HD\u2010MTX developed acute hepatotoxicity with elevated alanine aminotransferase (ALT) levels. Most patients with Grade 3\u20134 ALT elevation failed to recover to Grade 2 within 7\u2009days. Women and children are high\u2010risk subgroups for HD\u2010MTX\u2010mediated elevation of ALT levels. Age is a factor that contributes to the pharmacokinetic differences of HD\u2010MTX. However, the concurrent use of PPIs, TMP\u2010SMX, or NSAIDs did not affect the elimination of MTX when administered with adequate supportive therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Co\u2010administration of PPIs, TMP\u2010SMX, or NSAIDs may have limited effects on acute hepatotoxicity in well\u2010monitored and adequately pre\u2010medicated patients with OGS undergoing chemotherapy with HD\u2010MTX. Clinicians should pay particular attention to ALT levels when prescribing HD\u2010MTX to children and women.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5936","type":"journal-article","created":{"date-parts":[[2023,4,16]],"date-time":"2023-04-16T20:45:56Z","timestamp":1681677956000},"page":"12354-12364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effect of c<scp>o\u2010medications<\/scp> and potential risk factors of <scp>high\u2010dose methotrexate\u2010mediated<\/scp> acute hepatotoxicity in patients with osteosarcoma"],"prefix":"10.1002","volume":"12","author":[{"given":"Sheng\u2010Fan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Department and Institute of Pharmacology College of Medicine, National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Department of Clinical Pharmacy, School of Pharmacy Taipei Medical University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan\u2010Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department and Institute of Pharmacology College of Medicine, National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueh\u2010Ching","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Department and Institute of Pharmacology College of Medicine, National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Department of Clinical Pharmacy, School of Pharmacy Taipei Medical University  Taipei Taiwan"},{"name":"Department of Pharmacy, School of Pharmaceutical Sciences National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin\u2010Chen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department and Institute of Pharmacology College of Medicine, National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Department of Pharmacy, School of Pharmaceutical Sciences National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po\u2010Kuei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Joint Reconstruction Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Therapeutical and Research Center of Musculoskeletal Tumor Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Institute of Clinical Medicine, School of Medicine National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Orthopedic Department of Medicine National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Joint Reconstruction Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Therapeutical and Research Center of Musculoskeletal Tumor Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Institute of Clinical Medicine, School of Medicine National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Orthopedic Department of Medicine National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0738-4700","authenticated-orcid":false,"given":"Giun\u2010Yi","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"School of Medicine College of Medicine, National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuh\u2010Lih","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Department and Institute of Pharmacology College of Medicine, National Yang Ming Chiao Tung University  Taipei Taiwan"},{"name":"Department of Pharmacy, School of Pharmaceutical Sciences National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a011577"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-014-3697-3"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2010.02.003"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24121"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-0284-9_1"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000003420"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2018.11.027"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-014-4154-z"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30214-5"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3747\/co.21.1973"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2010.05.010"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872-034X.2007.00170.x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1179\/1973947812Y.0000000055"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00776-009-1347-6"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.6.5.635"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015-0164"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.11-6-694"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.7.1443"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-11-268"},{"issue":"9","key":"e_1_2_12_21_1","first-page":"3807","article-title":"Delayed elimination of methotrexate associated with co\u2010administration of proton pump inhibitors","volume":"30","author":"Santucci R","year":"2010","journal-title":"Anticancer Res"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)83351-7"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)90910-4"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197801)41:1<36::AID-CNCR2820410108>3.0.CO;2-I"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/15563650.2018.1484128"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-012-1214-2"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.04054.x"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03303.x"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12384"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1586\/ecp.11.57"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270004268128"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000606"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)90786-5"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20152"},{"issue":"3","key":"e_1_2_12_35_1","first-page":"405","article-title":"Age\u2010related pharmacokinetics of high\u2010dose methotrexate in patients with osteosarcoma","volume":"63","author":"Wang YM","year":"1979","journal-title":"Cancer Treat Rep"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.43.8598"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.5936","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:47:14Z","timestamp":1697071634000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.5936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,16]]},"references-count":35,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/cam4.5936"],"URL":"https:\/\/doi.org\/10.1002\/cam4.5936","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,16]]},"assertion":[{"value":"2023-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}