甲氨蝶呤、多柔比星和顺铂对比甲氨蝶呤、多柔比星和顺铂联合异环磷酰胺用于新诊断的高级别骨肉瘤术前化疗反应不佳者（JCOG0905）：一项多中心、开放标签、随机试验
Methotrexate, Doxorubicin, and Cisplatin Versus Methotrexate, Doxorubicin, and Cisplatin + Ifosfamide in Poor Responders to Preoperative Chemotherapy for Newly Diagnosed High-Grade Osteosarcoma (JCOG0905): A Multicenter, Open-Label, Randomized Trial.
作者信息
Hiraga Hiroaki, Machida Ryunosuke, Kawai Akira, Kunisada Toshiyuki, Yonemoto Tsukasa, Endo Makoto, Nishida Yoshihiro, Nagano Akihito, Ae Keisuke, Yoshida Shinichirou, Asanuma Kunihiro, Toguchida Junya, Furuta Taisuke, Nakayama Robert, Akisue Toshihiro, Hiruma Toru, Morii Takeshi, Nishimura Hideki, Hiraoka Koji, Takeyama Masanobu, Emori Makoto, Tsukushi Satoshi, Hatano Hiroshi, Kawashima Hiroyuki, Isu Kazuo, Tanaka Kazuhiro, Kataoka Tomoko, Fukuda Haruhiko, Iwamoto Yukihide, Ozaki Toshifumi
机构信息
Musculoskeletal Oncology, NHO Hokkaido Cancer Center, Sapporo, Japan.
Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan.
出版信息
J Clin Oncol. 2025 Jun;43(16):1886-1897. doi: 10.1200/JCO-24-01281. Epub 2025 Mar 26.
PURPOSE
Our previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m [4g/m once on day 1, then 2g/m once on days 2-7] × six) to patients showing a poor response (PrRsp) to preoperative chemotherapy with methotrexate, doxorubicin, and cisplatin (MAP) improves their prognoses. In this Japan Clinical Oncology Group (JCOG) study, JCOG0905, we aimed to investigate the efficacy and safety of IF in patients with PrRsp.
METHODS
JCOG0905 is a multicenter, open-label, multi-institutional, randomized trial. Eligible patients (50 years and younger) had resectable, high-grade osteosarcoma (stage II or III, Union for International Cancer Control TNM) of the extremities, limb girdles, and thoracic wall. After two MAP cycles and tumor resection, patients with PrRsp were randomly assigned to either the MAP or MAP plus 15 g/m (3g/m once daily on days 1-5) × six IF (MAP + IF [MAPIF]) group. The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The planned sample size was 100 patients with a one-sided α of .1 and a power of 0.7, assuming a 3-year DFS of 50% and 65% for MAP and MAPIF, respectively. This trial is registered with the Japan Registry of Clinical Trials (jRCT; jRCTs031180126).
RESULTS
Of the 287 patients registered between February 2010 and August 2020, 51 and 52 patients with PrRsp were assigned to the MAP and MAPIF groups, respectively. As of March 2022, DFS did not differ between groups (hazard ratio [HR], 1.05 [95% CI, 0.55 to 1.98]) and OS was numerically inferior in the MAPIF group (HR, 1.48 [95% CI, 0.68 to 3.22]). Nine and zero patients in the MAPIF and MAP groups discontinued treatment because of adverse events, respectively.
CONCLUSION
Evidence from JCOG0905 does not support the addition of IF for patients with PrRsp.
目的
我们之前关于高级别骨肉瘤的NECO II期研究表明，对于术前使用甲氨蝶呤、阿霉素和顺铂（MAP）化疗反应不佳（PrRsp）的患者，给予异环磷酰胺（IF；16 g/m[第1天单次给予4g/m，然后在第2 - 7天每天单次给予2g/m]×6个周期）可改善其预后。在这项日本临床肿瘤学会（JCOG）研究JCOG0905中，我们旨在研究IF对PrRsp患者的疗效和安全性。
方法
JCOG0905是一项多中心、开放标签、多机构的随机试验。符合条件的患者（50岁及以下）患有可切除的四肢、肢带和胸壁高级别骨肉瘤（国际癌症控制联盟TNM分期II期或III期）。在两个MAP周期和肿瘤切除术后，PrRsp患者被随机分配至MAP组或MAP加15 g/m（第1 - 5天每天单次给予3g/m）×6个周期IF的MAP加IF（MAPIF）组。主要终点是无病生存期（DFS）；次要终点是总生存期（OS）和安全性。计划样本量为100例患者，单侧α为0.1，检验效能为0.7，假设MAP组和MAPIF组的3年DFS分别为50%和65%。本试验已在日本临床试验注册中心（jRCT；jRCTs031180126）注册。
结果
在2010年2月至2020年8月登记的287例患者中，分别有51例和52例PrRsp患者被分配至MAP组和MAPIF组。截至2022年3月，两组间DFS无差异（风险比[HR]，1.05[95%CI，0.55至1.98]），MAPIF组的OS在数值上较低（HR，1.48[95%CI，0.68至3.22]）。MAPIF组和MAP组分别有9例和0例患者因不良事件停止治疗。
结论
JCOG0905的证据不支持对PrRsp患者加用IF。
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