Korean J Pediatr.  2009 May;52(5):581-587. 10.3345/kjp.2009.52.5.581.

Serum methotrexate level is inversely related to the outcome of osteosarcoma patients

• Lee JA
• Kim MS
• Lee JK
• Kim DH
• Hong YJ
• Song WS
• Cho WH
• Lee SY
• Lim JS
• Park KD
• Jeon DG

• KMID: 2281462
• DOI: http://doi.org/10.3345/kjp.2009.52.5.581

Abstract

PURPOSE
To evaluate the correlation between serum methotrexate (MTX) peak levels and clinical outcome of osteosarcoma, as well as to determine the correlation of these levels with the histologic response and event-free survival (EFS). METHODS: To maintain the homogeneity of the study population, we selected 52 patients with localized extremity osteosarcoma who had received two cycles of neoadjuvant chemotherapy consisting of high-dose (HD) MTX (12 g/m2), cisplatin (100 mg/m2), and doxorubicin (60 mg/m2). RESULTS: Totally, 204 courses of HD MTX were administered. The serial MTX levels (mean+/-SE) at 4 h (peak), 24 h, 48 h, and 72 h were 1292.14+/-12.83 micrometer, 9.29+/-3.89 micrometer, 1.73+/-1.37 micrometer, and 0.58+/-0.44 micrometer, respectively. The peak MTX serum level was 1292.14+/-12.83 micrometer. Neither the continuous average MTX peak level nor the dichotomized MTX peak level was related to the histologic response. However, the patients with a high 24-h MTX level (3.4 micrometer) had a poor histologic response (P=0.044). An inverse relationship was observed between MTX levels and survival: the EFS was better in the patients with a mean MTX peak level of less than 1,400 micrometer (P=0.002) and mean 24-h MTX level of less than 3.4 micrometer (P=0.011). CONCLUSION: The inverse correlation between the MTX level and the outcome is an unexpected finding. Further study on the pharmacokinetics of MTX is required to substantiate our findings and elucidate the mechanism involved.

Keyword

Osteosarcoma; Methotrexate (MTX); Serum level; Outcome

MeSH Terms

Cisplatin
Disease-Free Survival
Doxorubicin
Extremities
Humans
Methotrexate
Osteosarcoma
Cisplatin
Doxorubicin
Methotrexate