Details

Autor(en) / Beteiligte

• Hegyi, Marta
• Gulácsi, Ágnes
• Cságoly, Edit
• Csordás, Katalin
• Eipel, Olivér T.
• Erdélyi, Dániel J.
• Müller, Judit
• Nemes, Karolina
• Lautner-Csorba, Orsolya
• Kovács, Gábor T.

Titel

Clinical relations of methotrexate pharmacokinetics in the treatment for pediatric osteosarcoma

Ist Teil von

• Journal of cancer research and clinical oncology, 2012-10, Vol.138 (10), p.1697-1702

Ort / Verlag

Berlin/Heidelberg: Springer-Verlag

Erscheinungsjahr

2012

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• 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.