All issues > Volume 52(5); 2009

Original Article

Korean J Pediatr. 2009;52(5):581-587. Published online May 15, 2009.

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

Jun Ah JA Lee¹, Min Suk MS Kim³, Jin Kyung JK Lee⁴, Dong Ho DH Kim¹, Young Joon YJ Hong⁴, Won Seok WS Song², Wan Hyeong WH Cho², Soo-Yong SY Lee², Jung Sub JS Lim², Kyung Duk KD Park², Dae-Geun DG Jeon²

¹Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea
²Department of Orthopedic Surgery, Korea Cancer Center Hospital, Seoul, Korea
³Department of Pathology, Korea Cancer Center Hospital, Seoul, Korea
⁴Department of Laboratory Medicine, Korea Cancer Center Hospital, Seoul, Korea

Correspondence Dae-Geun DG Jeon ,Email: dgjeon@kcch.re.kr

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¡¾SE) at 4 h (peak), 24 h, 48 h, and 72 h were 1292.14¡¾12.83 µM, 9.29¡¾3.89 µM, 1.73¡¾1.37 µM, and 0.58¡¾0.44 µM, respectively. The peak MTX serum level was 1292.14¡¾12.83 µM. 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 µM) 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 µM (P=0.002) and mean 24-h MTX level of less than 3.4 µM (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.

Keywords :Osteosarcoma, Methotrexate (MTX), Serum level, Outcome