Pharmacokinetic individualization of high-dose methotrexate chemotherapy for the treatment of localized osteosarcoma

Y. Fujita, T. Nakamura, T. Aomori, H. Nishiba, T. Shinozaki, T. Yanagawa, K. Takagishi, H. Watanabe, Y. Okada, K. Nakamura, R. Horiuchi, Koujirou Yamamoto

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7 Citations (Scopus)


Individualization of high-dose methotrexate (MTX) dosing is important to achieve therapeutic levels (700-1,000 μM) for osteosarcoma. Therefore we developed a pharmacokinetically (PK) individualized dosage regimen to maintain MTX concentrations of 700 μM (1 h bolus followed by 5 h maintenance infusion) and evaluated its safety and efficacy. Loading and maintenance doses were calculated by the PK parameters based on 2-compartment model analysis. Thirty-two courses of chemotherapy were performed in 9 patients with osteosarcoma. The maximum concentrations during maintenance infusion in 31 courses (97%) were above 700 μM. Only 1 patient developed severe hepatotoxicity as adverse effect. Total body clearance of MTX decreased in 4 patients when weekly MTX chemotherapy was performed for 3 consecutive weeks. Although the clearance was changed, the average MTX concentrations were maintained at about 700 μM by the PK individualization. The 5-year survival rate was 77.8% (7 of 9 patients), and all of them have survived for more than 9 years. This PK individualization is safe and useful for tailoring high-dose MTX therapy to achieve therapeutic levels.

Original languageEnglish
Pages (from-to)186-190
Number of pages5
JournalJournal of Chemotherapy
Issue number3
Publication statusPublished - 2010 Jun
Externally publishedYes


  • 5-Year survival rate
  • Methotrexate
  • Osteosarcoma
  • Pharmacokinetic individualization

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases


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