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. PATIENTS AND 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.

Bone Tumor Reference Center at the Institute of Pathology University Hospital Basel Basel Switzerland

British Columbia Children's Hospital University of British Columbia Vancouver Canada

Center for Clinical Trials University Hospital Münster Münster Germany

Children's Hospital of Philadelphia University of Pennsylvania School of Medicine Philadelphia

Children's Oncology Group Arcadia USA

Cincinnati Children's Hospital Medical Center Cincinnati

Cooperative Osteosarcoma Study Group Klinikum Stuttgart Olgahospital Stuttgart Germany

Dana Farber Cancer Institute Boston

Department of General Orthopedics and Tumor Orthopedics University Hospital Muenster Muenster Germany

Department of Oncology Oslo University Hospital Norwegian Radium Hospital Scandinavian Sarcoma Group Oslo Norway

Department of Oncology University College Hospital London UK

Department of Pathology Boston Children's Hospital Boston USA

Department of Pediatric Hematology Oncology University Hospital Prague Czech Republic

Department of Pediatric Radiology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Pediatrics and Medical Oncology Leiden University Medical Center Leiden The Netherlands

Department of Radiation Oncology Medical Center Hamburg Eppendorf Hamburg Germany

Division of Cancer Surgery and Transplantation and Scandinavian Sarcoma Group Oslo University Hospital Oslo Institute for Clinical Medicine University of Oslo Oslo Norway

H Lee Moffit Cancer Centre and Research Institute Tampa

IWK Health Center Dalhousie University Halifax Canada

Lucile Salter Packard Childrens Hospital Stanford Palo Alto USA

Mayo Clinic Rochester USA

Medical Research Council Clinical Trials Unit at University College London London UK

Memorial Sloan Kettering Cancer Center New?York

Memorial Sloan Kettering Cancer Center New?York Orthopedic Surgery Johns Hopkins Baltimore USA

Our Lady's Children's Hospital Dublin Ireland

Primary Children's Hospital and Huntsman Cancer Institute University of Utah Salt Lake City

Royal National Orthopaedic Hospital Stanmore Cancer Institute University College London London UK

Royal Orthopaedic Hospital Birmingham UK

Section of Pediatric Hematology Oncology Montefiore Medical Center Bronx USA

Skane University Hospital Lund University Lund Sweden

St Anna Children's Hospital Vienna Austria

Stanford University Medical Center Pediatric Hematology Oncology Palo Alto USA

Texas Children's Cancer Centre Baylor College of Medicine Houston

University Children's Hospital Basel Basel Switzerland

University Hospital Ghent Gent Belgium

University Hospital of Muenster Muenster Germany

University of Helsinki and HUSLAB Helsinki Finland

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Osteosarcomas of the hand and foot: A sarcoma‑center case series experience

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Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial

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ClinicalTrials.gov
NCT00134030