Choeyprasert Worawut, Pakakasama Samart, Sirachainan Nongnuch, Songdej Duantida, Chuansumrit Ampaiwan, Anurathapan Usanarat, Hongeng Suradej, Nartthanarung Adisak
Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Thailand E-mail :
Asian Pac J Cancer Prev. 2014;15(22):9823-9. doi: 10.7314/apjcp.2014.15.22.9823.
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).
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).
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.
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±6.0% and 53.2±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±10.5%, 79.8±9.1% for MTX(+) and 31.1±6.9%, 42.2±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±13.6% and 15.0±8.0% for 3-year DFS, p=0.010, 73.3±13.2% and 20±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).
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.
大剂量甲氨蝶呤（HD-MTX）被认为是与顺铂（CDP）、卡铂（CBDCA）、阿霉素（ADM）、依托泊苷（VP-16）和异环磷酰胺（IFO）等其他药物联合用于治疗小儿骨肉瘤的有效治疗成分。
在拉玛提博迪医院（1999 - 2014年）证明HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)]方案与CDP/ADM/CBDCA/IFO [MTX(-)]方案治疗儿童骨肉瘤具有可比性的可行性和有效性。
对1999年至2014年间接受两种化疗方案治疗的18岁以下骨肉瘤患者进行回顾性分析。共有45例患者接受MTX(-)方案，21例接受MTX(+)方案。
总体保肢率和截肢率分别为12.9%和77.7%。无论治疗方案如何，3年无病生存率（DFS）和总生存率（OS）的Kaplan-Meier分析结果分别为43.4±6.0%和53.2±6.1%。与MTX(-)方案相比，MTX(+)方案的3年DFS和OS有显著改善（p = 0.010和p = 0.009，对数秩检验）[MTX(+)方案分别为69.8±10.5%，79.8±9.1%；MTX(-)方案分别为31.1±6.9%，42.2±7.4%]。接受MTX(+)方案治疗的转移性骨肉瘤患者的3年DFS和OS在统计学上显著高于接受MTX(-)方案治疗的患者（3年DFS分别为66.7±13.6%和15.0±8.0%，p = 0.010；3年OS分别为73.3±13.2%和20±8.9%，p = 0.006）。3年DFS和OS较差的独立危险因素是组织学反应差（肿瘤坏死<90%）和采用MTX(-)方案治疗。多因素分析仅确定采用MTX(-)方案治疗是OS较差的独立预测因素，风险比（HR）为3.53（95%置信区间为l.2 - 至10.41，p = 0.022）。
我们的研究证明了基于HD-MTX方案的耐受性性、可行性和有效性，提高了小儿骨肉瘤病例的生存率，这与发达国家的报道一致。
