title: EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.
abstract: BACKGROUND
  Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response.
  
  
  METHODS
  Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken.
  
  
  RESULTS
  Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen.
  
  
  CONCLUSIONS
  New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.
authors.affiliation: Department of Oncology, University College Hospital, London, UK.
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authors.initials: JS
authors.lastname: Whelan
authors.affiliation: Cooperative Osteosarcoma Study Group (COSS), Klinikum Stuttgart - Olgahospital, Stuttgart, Germany.
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authors.initials: SS
authors.lastname: Bielack
authors.affiliation: Stanford University Medical Center, Pediatric Hematology/Oncology, Palo Alto, USA.
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authors.lastname: Marina
authors.affiliation: Division of Cancer, Surgery and Transplantation, and Scandinavian Sarcoma Group, Oslo University Hospital, Oslo Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
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authors.lastname: Smeland
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
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authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK.
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authors.affiliation: Department of Pediatrics and Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
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authors.affiliation: Center for Clinical Trials, University Hospital Münster, Münster, Germany.
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authors.affiliation: University of Helsinki and HUSLAB, Helsinki, Finland.
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authors.affiliation: University Hospital of Muenster, Muenster, Germany.
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authors.affiliation: Lucile Salter Packard Childrens Hospital Stanford, Palo Alto, USA.
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authors.affiliation: University Hospital Ghent, Gent, Belgium.
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authors.affiliation: Department of Pediatrics and Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
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authors.affiliation: Department of General Orthopedics and Tumor Orthopedics, University Hospital Muenster, Muenster, Germany.
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authors.lastname: Gosheger
authors.affiliation: Royal Orthopaedic Hospital, Birmingham, UK.
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authors.initials: RJ
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authors.affiliation: Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, Scandinavian Sarcoma Group, Oslo, Norway.
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authors.initials: KS
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authors.affiliation: Department of Pediatric Radiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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authors.initials: PC
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authors.initials: RL
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authors.lastname: Schwarz
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authors.initials: LA
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authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, London, UK m.sydes@ucl.ac.uk.
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authors.initials: MR
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mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000601:surgery; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000188:drug therapy* / Q000601:surgery; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011788:Quality of Life; D012107:Research Design; D055815:Young Adult
chemical_list: D016898:Interferon-alpha; C571406:PEG-IFN-SA; D011092:Polyethylene Glycols; D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate
keywords: international collaboration; osteosarcoma; randomised controlled trial; trial conduct