High dose methotrexate in adult patients with osteosarcoma: Clinical and pharmacokinetic results

Alessandro Comandone, Roberto Passera, Antonella Boglione, Valentina Tagini, Stefano Ferrari, Luigi Cattel

Research output: Contribution to journalArticle

Abstract

High dose methotrexate (HDMTX) with folinic acid rescue is widely used to treat osteosarcoma, which predominantly afflicts children; the study investigated HDMTX pharmacokinetics (pk) in adult subjects in neoadjuvant/adjuvant settings. Twenty five patients with advanced osteosarcoma (11 females - 14 males, median age 26.0 years) were treated by 12 g/m 2 HDMTX 4 hour iv infusion (64 total courses, range 1-7 courses). Pk was determined by non-compartmental analysis and population pk modeling. Median (range) bioavailability pk parameters were: Cmax (maximum MTX concentration) 1149.5 μM (692-2 200), AUCtot (total area under curve) 6 955.1 μmol*h/l (3 477-12 681). Cmax > 1 000 μM gave increased histological responses (p el). Toxicity was mild: only two reversible G4 events were observed, related to AUQ tot > 12 000 μmol*h/l (p max/AUCtot and subject age/sex was found, even in the population pk model. The excretion mechanism is not affected by sex/age differences. HDMTX can safely be administered to adults: as in younger patients, a good clinical response can be predicted by Cmax, while severe toxicity depends on highest AUCtot values.

Original languageEnglish
Pages (from-to)406-411
Number of pages6
JournalActa Oncologica
Volume44
Issue number4
DOIs
Publication statusPublished - 2005

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'High dose methotrexate in adult patients with osteosarcoma: Clinical and pharmacokinetic results'. Together they form a unique fingerprint.

  • Cite this

    Comandone, A., Passera, R., Boglione, A., Tagini, V., Ferrari, S., & Cattel, L. (2005). High dose methotrexate in adult patients with osteosarcoma: Clinical and pharmacokinetic results. Acta Oncologica, 44(4), 406-411. https://doi.org/10.1080/02841860510029770