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http://dx.doi.org/10.7314/APJCP.2014.15.22.9823

Comparative Outcome of Thai Pediatric Osteosarcoma Treated with Two Protocols: the Role of High-Dose Methotrexate (HDMTX) in a Single Institute Experience  

Choeyprasert, Worawut (Department of Pediatrics, Faculty of Medicine, Chiang Mai University)
Pakakasama, Samart (Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University)
Sirachainan, Nongnuch (Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University)
Songdej, Duantida (Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University)
Chuansumrit, Ampaiwan (Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University)
Anurathapan, Usanarat (Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University)
Hongeng, Suradej (Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University)
Nartthanarung, Adisak (Department of Orthopedics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.22, 2014 , pp. 9823-9829 More about this Journal
Abstract
Background: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). Objectives: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). Materials and Methods: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. Results: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan-Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were $43.4{\pm}6.0%$ and $53.2{\pm}6.1%$ respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [$69.8{\pm}10.5%$, $79.8{\pm}9.1%$ for MTX(+) and $31.1{\pm}6.9%$, $42.2{\pm}7.4%$ for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol ($66.7{\pm}13.6%$ and $15.0{\pm}8.0%$ for 3-year DFS, p=0.010, $73.3{\pm}13.2%$ and $20{\pm}8.9%$ for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). Conclusions: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.
Keywords
Pediatric osteosarcoma; methotrexate; outcome; survival; Thailand;
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