dc.contributor.author |
Hegyi, Márta |
|
dc.contributor.author |
Gulácsi A |
|
dc.contributor.author |
Cságoly E |
|
dc.contributor.author |
Csordas, Katalin |
|
dc.contributor.author |
Eipel, Olivér |
|
dc.contributor.author |
Erdélyi, Dániel |
|
dc.contributor.author |
Müller, Judit |
|
dc.contributor.author |
Nemes, Karolina |
|
dc.contributor.author |
Lautner-Csorba, Orsolya |
|
dc.contributor.author |
Kovács, Gábor |
|
dc.date.accessioned |
2016-10-12T12:41:00Z |
|
dc.date.available |
2016-10-12T12:41:00Z |
|
dc.date.issued |
2012 |
|
dc.identifier |
84866735479 |
|
dc.identifier.citation |
pagination=1697-1702;
journalVolume=138;
journalIssueNumber=10;
journalTitle=JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/3727 |
|
dc.identifier.uri |
doi:10.1007/s00432-012-1214-2 |
|
dc.description.abstract |
Purpose: High-dose methotrexate (HD-MTX) with leucovorin rescue is widely used to treat osteosarcoma. Our objectives were to assess correlations between pharmacokinetic parameters and the outcome of osteosarcoma and to analyze the relation between HD-MTX exposure and toxicity. Methods: Pharmacokinetic data of 105 patients with osteosarcoma treated with 989 HD-MTX courses were evaluated. Pharmacokinetic parameters (clearance, half-life and AUC) were calculated based on methotrexate (MTX) serum levels measured at 6, 24, 36, 48 h after the initiation of the infusion. Clinical data were collected by retrospective chart review. Hepato-, nephro- and bone marrow toxicity parameters were categorized according to Common Toxicity Criteria v.3.0, and MTX dose intensity was calculated. Event-free survival (EFS) and overall survival (OS) were estimated according to the Kaplan-Meier method. Results: Patients with serious hepatotoxicity had higher mean peak MTX concentrations (p < 0.0001), 24-h (p = 0.001) and 48-h MTX serum levels (p = 0.008) and AUC 0-48 (p < 0.0001), and lower MTX clearance (p = 0.0002). No significant association was found between toxicity and age, gender, presence of metastases or histological tumor response. Patients with higher 48-h MTX serum levels had significantly better OS and EFS. Higher dose intensity was associated with better EFS (p = 0.0504). There was no association between presence of toxicity and survival. Conclusion: There was correlation between MTX exposure and the incidence of toxicity. Higher serum concentrations at 48 h were associated with a better 5-year OS and EFS. These results suggest that higher MTX exposure may lead to serious side effects, but it also improves treatment outcome. © 2012 Springer-Verlag. |
|
dc.relation.ispartof |
urn:issn:0171-5216 |
|
dc.title |
Clinical relations of methotrexate pharmacokinetics in the treatment for pediatric osteosarcoma |
|
dc.type |
Journal Article |
|
dc.date.updated |
2016-10-06T10:53:47Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
2045370 |
|
dc.identifier.wos |
000309101600012 |
|
dc.identifier.pubmed |
22652833 |
|
dc.contributor.department |
SE/AOK/K/II. Sz. Gyermekgyógyászati Klinika |
|
dc.contributor.department |
SE/AOK/I/Genetikai, Sejt- és Immunbiológiai Intézet |
|
dc.contributor.institution |
Semmelweis Egyetem |
|