Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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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)
  • Published : 2014.12.18
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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.

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