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.

IF 42.1 1区医学 Q1 ONCOLOGY

Journal of Clinical Oncology Pub Date : 2025-06-01 Epub Date: 2025-03-26 DOI:10.1200/JCO-24-01281

Hiroaki Hiraga, Ryunosuke Machida, Akira Kawai, Toshiyuki Kunisada, Tsukasa Yonemoto, Makoto Endo, Yoshihiro Nishida, Akihito Nagano, Keisuke Ae, Shinichirou Yoshida, Kunihiro Asanuma, Junya Toguchida, Taisuke Furuta, Robert Nakayama, Toshihiro Akisue, Toru Hiruma, Takeshi Morii, Hideki Nishimura, Koji Hiraoka, Masanobu Takeyama, Makoto Emori, Satoshi Tsukushi, Hiroshi Hatano, Hiroyuki Kawashima, Kazuo Isu, Kazuhiro Tanaka, Tomoko Kataoka, Haruhiko Fukuda, Yukihide Iwamoto, Toshifumi Ozaki

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引用次数: 0

Abstract

Purpose: Our previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m² [4g/m² once on day 1, then 2g/m² 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/m² (3g/m² 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.

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甲氨蝶呤、阿霉素和顺铂与甲氨蝶呤、阿霉素和顺铂+异环磷酰胺对新诊断的高级别骨肉瘤术前化疗不良反应（JCOG0905）：一项多中心、开放标签、随机试验

目的：我们之前对高级别骨肉瘤的NECO II期研究表明，使用异环磷酰胺(IF；16 g/m2 [4g/m2第1天1次，然后2g/m2第2-7天1次]× 6)对术前甲氨蝶呤、阿霉素和顺铂（MAP）化疗反应不良（PrRsp）的患者改善其预后。在这项日本临床肿瘤组（JCOG）的JCOG0905研究中，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、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（II期或III期，国际癌症控制联盟TNM）。在两个MAP周期和肿瘤切除后，PrRsp患者被随机分配到MAP组或MAP + 15 g/m2 （3g/m2每日1次，第1-5天）× 6 IF （MAP + IF [MAPIF]）组。主要终点为无病生存期（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，幂为0.7，假设MAP和MAPIF的3年DFS分别为50%和65%。该试验已在日本临床试验注册中心(jRCT；jRCTs031180126)。结果：在2010年2月至2020年8月登记的287例患者中，51例和52例PrRsp患者分别被分配到MAP组和MAPIF组。截至2022年3月，两组间的DFS没有差异（风险比[HR]， 1.05 [95% CI， 0.55至1.98]），MAPIF组的OS在数字上较差（HR, 1.48 [95% CI， 0.68至3.22]）。MAPIF组和MAP组分别有9例和0例患者因不良事件而停止治疗。结论：JCOG0905的证据不支持在PrRsp患者中添加IF。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.