title: Delayed High-dose Methotrexate Excretion and Influencing Factors in Osteosarcoma Patients.
abstract: BACKGROUND
  High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is "gold standard" therapy for osteosarcoma. Plasma concentrations of methotrexate (MTX) are closely related to its efficacy and toxicity. Delayed excretion of MTX can lead to serious adverse reactions that may result in treatment cessation, irreversible organ damage, and death. This study focused on the incidence of delayed excretion of MTX in Chinese osteosarcoma patients.
  
  
  METHODS
  A total of 1277 osteosarcoma patients were treated with HD-MTX chemotherapy (4291 cycles) from 2010 to 2015. Factors that could influence delayed excretion of MTX (gender, age, number of chemotherapy cycles, and serum concentration of MTX) were analyzed.
  
  
  RESULTS
  The incidence of delayed excretion of MTX (serum concentrations at 24 h [C24 h] >5 μmol/L) and severe delayed excretion of MTX (C24 h >20 μmol/L) were 6.19% and 0.86% per patient, and 2.31% and 0.26% per cycle of treatment, respectively. The incidence of severe delayed excretion of MTX was associated with gender, age, and C24 h.
  
  
  CONCLUSIONS
  Precaution of delayed excretion of MTX is needed during osteosarcoma treatment using HD-MTX. An optimal individualized rescue strategy can be created with consideration of gender, age, and C24 h.
authors: Department of Clinical Pharmacology, Beijing Jishuitan Hospital, Beijing 100035, China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Orthopaedic Oncology, Beijing Jishuitan Hospital, Beijing 100035, China.
authors: Qing
authors: Q
authors: Zhang
authors: Department of Clinical Pharmacology, Beijing Jishuitan Hospital, Beijing 100035, China.
authors: Ting-Ting
authors: TT
authors: Zheng
authors: Department of Clinical Pharmacology, Beijing Jishuitan Hospital, Beijing 100035, China.
authors: Jian-Cun
authors: JC
authors: Zhen
authors: Department of Orthopaedic Oncology, Beijing Jishuitan Hospital, Beijing 100035, China.
authors: Xiao-Hui
authors: XH
authors: Niu
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000097:blood / Q000188:drug therapy*; D012189:Retrospective Studies; D012737:Sex Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D008727:Methotrexate