title: Comprehensive analysis of published phase I/II clinical trials between 1990-2010 in osteosarcoma and Ewing sarcoma confirms limited outcomes and need for translational investment.
abstract: BACKGROUND
  High grade primary bone sarcomas are rare cancers that affect mostly children and young adults. Osteosarcoma and Ewing sarcoma are the most common histological subtypes in this age group, with current multimodality treatment strategies achieving 55-70% overall survival. As there remains an urgent need to develop new therapeutic interventions, we have reviewed published phase I/II trials that have been reported for osteosarcoma and Ewing sarcoma in the last twenty years.
  
  
  RESULTS
  We conducted a literature search for clinical trials between 1990 and 2010, either for trials enrolling bone sarcoma patients as part of a general sarcoma indication or trials specifically in osteosarcoma and Ewing sarcoma. We identified 42 clinical trials that fulfilled our search criteria for general sarcoma that enrolled these patient groups, and eight and twenty specific trials for Ewing and osteosarcoma patients, respectively. For the phase I trials which enrolled different tumour types our results were incomplete, because the sarcoma patients were not mentioned in the PubMed abstract. A total of 3,736 sarcoma patients were included in these trials over this period, 1,114 for osteosarcoma and 1,263 for Ewing sarcoma. As a proportion of the worldwide disease burden over this period, these numbers reflect a very small percentage of the potential patient recruitment, approximately 0.6% for Ewing sarcoma and 0.2% for osteosarcoma. However, these data show an increase in recent activity overall and suggest there is still much room for improvement in the current trial development structures.
  
  
  CONCLUSIONS
  Lack of resources and commercial investment will inevitably limit opportunity to develop sufficiently rapid improvements in clinical outcomes. International collaboration exists in many well founded co-operative groups for phase III trials, but progress may be more effective if there were also more investment of molecular and translational research into disease focused phase I/II clinical trials. Examples of new models for early translational and early phase trial collaboration include the European based EuroBoNeT network, the Sarcoma Alliance for Research through Collaboration network (SARC) and the new European collaborative translational trial network, EuroSarc.
authors.affiliation: Department of Oncology, Oxford Cancer and Haematology Centre, Churchill Hospital, University of Oxford, Oxford OX3 7LJ, UK.
authors.forename: Annemiek M
authors.initials: AM
authors.lastname: van Maldegem
authors.affiliation: Department of Oncology, Oxford Cancer and Haematology Centre, Churchill Hospital, University of Oxford, Oxford OX3 7LJ, UK.
authors.forename: Aparna
authors.initials: A
authors.lastname: Bhosale
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, PO Box 9600, 2600 RC Leiden, The Netherlands.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Gelderblom
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, PO Box 9600, 2600 RC Leiden, The Netherlands.
authors.forename: Pancras Cw
authors.initials: PC
authors.lastname: Hogendoorn
authors.affiliation: Department of Oncology, Oxford Cancer and Haematology Centre, Churchill Hospital, University of Oxford, Oxford OX3 7LJ, UK.|Sir William Dunn School of Pathology, South Parks Road, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Hassan