Korean Journal of Pediatrics 2009;52(5):581-587.
Published online May 15, 2009.
Serum methotrexate level is inversely related to the outcome of osteosarcoma patients
Jun Ah Lee1, Min Suk Kim3, Jin Kyung Lee4, Dong Ho Kim1, Young Joon Hong4, Won Seok Song2, Wan Hyeong Cho2, Soo-Yong Lee2, Jung Sub Lim2, Kyung Duk Park2, Dae-Geun 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
혈중 methotrexate 농도와 골육종 환자들의 치료결과의 연관성
이준아1, 김민석3, 이진경4, 김동호1, 홍영준4, 송원석2, 조완형2, 이수용2, 임중섭2, 박경덕2, 전대근2
1원자력병원 소아청소년과
2원자력병원 소아청소년과
3원자력병원 병리과
4원자력병원 진단검사의학과
Correspondence: 
Dae-Geun 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.
Key Words: Osteosarcoma, Methotrexate (MTX), Serum level, Outcome


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