Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper session: Sarcoma

1482O - A phase III study comparing methotrexate (M), adriamycin (A) and cisplatin (P) with MAP + ifosfamide (MAP + IF) for the treatment of osteosarcoma: JCOG0905


10 Sep 2022


Proffered Paper session: Sarcoma


Clinical Research;  Cytotoxic Therapy;  Cancers in Adolescents and Young Adults (AYA)

Tumour Site

Bone Sarcomas


Hiroaki Hiraga


Annals of Oncology (2022) 33 (suppl_7): S681-S700. 10.1016/annonc/annonc1073


H. Hiraga1, R. Machida2, A. Kawai3, Y. Matsumoto4, T. Yonemoto5, Y. Nishida6, A. Nagano7, K. Ae8, S. Yoshida9, K. Asanuma10, J. Toguchida11, D. Huruta12, R. Nakayama13, T. Akisue14, T. Hiruma15, T. Morii16, K. Tanaka17, T. Kataoka18, H. Fukuda2, T. Ozaki19

Author affiliations

  • 1 Musculoskeletal Oncology, National Hospital Organization, Hokkaido Cancer Center, 003-0804 - Sapporo/JP
  • 2 Japan Clinical Oncology Group Data Center/operations Office, NCCH - National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 3 Musculoskeletal Oncology Dept., NCCH - National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 4 Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 812-8582 - Fukuoka/JP
  • 5 Orthopaedic Surgery, Chiba Cancer Center Hospital, 260-8717 - Chiba/JP
  • 6 Rehabilitation Medicine, Nagoya University Hospital, 466-8550 - Nagoya/JP
  • 7 Orthopaedic Surgery, Gifu University School of Medicine, 501-1193 - Gifu/JP
  • 8 Orthopaedic Surgery, Cancer Institute Hospotal of JFCR, 135-8550 - Tokyo/JP
  • 9 Orthopaedic Surgery, Tohoku University Hospital, 980-8575 - Sendai/JP
  • 10 Orthopaedic Surgery, Mie University Hospital, 514-8507 - Tsu/JP
  • 11 Center For Ips Cell Research And Application, Kyoto University, 606-8501 - Kyoto/JP
  • 12 Orthopaedic Surgery, Hiroshima University Hospital, 734-8551 - Hiroshima/JP
  • 13 Orthopaedic Surgery, Keio University School of Medicine, 160-8582 - Shinjuku-ku/JP
  • 14 Orthopaedic Surgery, Kobe University Graduate School of Medicine, 650-0017 - Kobe/JP
  • 15 Bone And Soft Tissue Tumor Surgery, Kanagawa Cancer Center, 2410815 - Yokohama/JP
  • 16 Orthopaedic Surgery, Kyorin University Faculty of Medicine, 181-0004 - Mitaka/JP
  • 17 Orthopaedic Surgery, Oita University Faculty of Medicine, 879-5593 - Yufu/JP
  • 18 Research Management Division, National Cancer Center - Tsukiji Campus, 104-0045 - Tokyo/JP
  • 19 Orthopaedic Surgery, Faculty of Medicine Dentistry and Pharmaceutical Sciences Okayama University, 700-8558 - Okayama/JP


Login to access the resources on OncologyPRO.

Abstract 1482O


Our previous phase II studies on high-grade osteosarcoma, NECO93J and 95J, suggested that application of Ifosfamide (IF) (16 g/m2 × 6 courses) to patients with a poor response (PrRsp) to preoperative chemotherapy using Methotrexate, Adriamycin, and Cisplatin (MAP) improves their prognosis. The JCOG0905 randomized controlled trial investigated the efficacy and safety of adding IF in patients with PrRsp (> 10% viable tumor cells at surgery).


Patients ≤ 50 years old with operable, high-grade osteosarcoma (Stage IIA, IIB, III, UICC TNM 6th edition) of the extremities, limb girdles, and thoracic wall were eligible for registration at diagnosis. Eligibility for randomization included: completion of 2 MAP cycles preoperatively, followed by complete resection of the primary tumor and 1 postoperative cycle of Adriamycin and Cisplatin with no disease progression; and known histological response. PrRsp patients were randomized (1:1) to continuation of MAP or MAP + IF (15 g/m2 × 6 courses). The primary endpoint was disease-free survival (DFS), and the secondary endpoints included overall survival (OS) and safety. The planned sample size was 100 with a one-sided alpha of 0.1 and power of 0.7, assuming 3-year DFS of MAP and MAP + IF of 50% and 65%, respectively.


Of the 287 patients registered from Feb. 2010 to Aug. 2020, 51 and 52 patients were randomly assigned to MAP and MAP + IF, respectively. At the second interim-analysis on March 2022, the 3-year DFS was 64.3% (95% confidence interval (CI) 49.4-75.8) in MAP and 64.3% (49.3-75.8) in MAP + IF (hazard ratio (HR) 1.05, 95% CI 0.57-1.91). The 3-year OS was 86.5% (72.4-93.7) in MAP and 78.8% (64.1-88.0) in MAP + IF (HR 1.48, 0.68-3.22). There were no treatment-related deaths in both arms. Nine patients in MAP + IF terminated protocol treatment due to adverse events, whereas none in MAP terminated treatment. Based on the results of this analysis, the Data and Safety Monitoring Committee of JCOG recommended terminating the study since the point estimate of HR was above the pre-specified HR of 1.0.


Evidence from JCOG0905 does not support adding IF in PrRsp patients, even at a total dose of 90 g/m2, which is higher than the dose of 60 g/m2 in EURAMOS-1.

Clinical trial identification

Editorial acknowledgement

Monisha R, MD, Forte Science Communications.

Legal entity responsible for the study

National Cancer Center.


the National Cancer Center Research and Development Fund (2020-J-3) and the Japan Agency for Medical Research and Development (AMED) under grant number JP20ck0106614.


All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.