Iwamoto Yukihide, Tanaka Kazuhiro, Isu Kazuo, Kawai Akira, Tatezaki Shin-ichiro, Ishii Takeshi, Kushida Kazuyoshi, Beppu Yasuo, Usui Masamichi, Tateishi Akio, Furuse Kiyoo, Minamizaki Takeshi, Kawaguchi Noriyoshi, Yamawaki Shinya
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan.
J Orthop Sci. 2009 Jul;14(4):397-404. doi: 10.1007/s00776-009-1347-6. Epub 2009 Aug 7.
Osteosarcoma is the most frequent primary malignant bone tumor. In Europe and the United States, its prognosis has been greatly improved by the use of multimodal treatment, including preoperative and postoperative chemotherapy as well as surgery. In Japan, however, only a few clinical studies on osteosarcoma have been carried out.
To evaluate the efficacy of neoadjuvant chemotherapy on nonmetastatic, operable osteosarcoma arising in the extremities, a prospective multi-institutional phase II trial, the Neoadjuvant Chemotherapy for Osteosarcoma (NECO) study, was conducted. Preoperative chemotherapy included high-dose methotrexate (HD-MTX), cisplatin (CDDP), and adriamycin (ADR). If the induction therapy was assessed as not effective, high-dose ifosfamide (IFO) was added to the chemotherapy regimen. A total of 124 patients were enrolled in this trial, and ultimately 113 patients were eligible.
The 5-year overall survival (OAS) and event-free survival (EFS) rates in the NECO study were 77.9% and 65.5%, respectively. A good histological response to the induction chemotherapy resulted in favorable OAS (78.7%). The patients assessed as poor histological responders with progressive disease after the induction chemotherapy exhibited comparable outcomes (OAS 89.5%, EFS 68.2%). There were no significant differences between the OAS and EFS rates of the patients in terms of response to preoperative chemotherapy.
We analyzed the results of the intensive neoadjuvant chemotherapy and the effects of adding IFO on patients with osteosarcoma in Japan. The results suggest efficacy of the high-dose IFO addition to the standard three-drug chemotherapy regimen. However, a randomized clinical study is needed to establish the true impact of IFO on patients with osteosarcoma.
骨肉瘤是最常见的原发性恶性骨肿瘤。在欧洲和美国，通过采用多模式治疗，包括术前和术后化疗以及手术，其预后已得到显著改善。然而，在日本，关于骨肉瘤的临床研究却很少。
为了评估新辅助化疗对四肢非转移性、可手术切除的骨肉瘤的疗效，开展了一项前瞻性多机构II期试验，即骨肉瘤新辅助化疗（NECO）研究。术前化疗包括大剂量甲氨蝶呤（HD-MTX）、顺铂（CDDP）和阿霉素（ADR）。如果诱导治疗被评估为无效，则在化疗方案中加入大剂量异环磷酰胺（IFO）。共有124例患者入组该试验，最终113例患者符合条件。
NECO研究中的5年总生存率（OAS）和无事件生存率（EFS）分别为77.9%和65.5%。对诱导化疗有良好组织学反应的患者总生存率良好（78.7%）。诱导化疗后被评估为组织学反应差且疾病进展的患者也表现出类似的结果（总生存率89.5%，无事件生存率68.2%）。术前化疗反应不同的患者在总生存率和无事件生存率方面没有显著差异。
我们分析了日本骨肉瘤患者强化新辅助化疗的结果以及添加IFO的效果。结果表明在标准的三药化疗方案中添加大剂量IFO是有效的。然而，需要进行一项随机临床研究来确定IFO对骨肉瘤患者的真正影响。
