Limits...
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.

van Maldegem AM, Bhosale A, Gelderblom HJ, Hogendoorn PC, Hassan AB - Clin Sarcoma Res (2012)

Bottom Line: 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 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oncology, Oxford Cancer and Haematology Centre, Churchill Hospital, University of Oxford, Oxford OX3 7LJ, UK. bass.hassan@path.ox.ac.uk.

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.

Conclusion: 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.

No MeSH data available.


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Flowchart diagrams of the clinical trial selection criteria outcomes for Ewing sarcoma (A) and osteosarcoma (B).
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Figure 1: Flowchart diagrams of the clinical trial selection criteria outcomes for Ewing sarcoma (A) and osteosarcoma (B).

Mentions: A flow-chart indicating the identification of clinical trials for inclusion in the analysis is reported for Ewing sarcoma (Figure 1A) and osteosarcoma (Figure 1B). During the search many reports had to be excluded because no results were published. When we searched the reports using full text, we had to exclude some papers because neither osteosarcoma nor Ewing sarcoma patients were included in these studies. When we combined the results, we identified 42 trials enrolling patients with any histological diagnosis of sarcoma that were eligible for our study, in that they included osteosarcoma and Ewing sarcoma. Of the 42 clinical trials twenty-one were phase I, two were phase I/II and nineteen were phase II trials. We found eight clinical trials which included only Ewing sarcoma patients; of this group two were phase I and six were phase II trials. We identified twenty trials that included only osteosarcoma patients. There were two phase I, sixteen were phase II and two were phase I/II trials. A total of 3,736 patients were included in all the clinical trials, of which 1,263 were Ewing sarcoma and 1,114 were osteosarcoma patients.


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.

van Maldegem AM, Bhosale A, Gelderblom HJ, Hogendoorn PC, Hassan AB - Clin Sarcoma Res (2012)

Flowchart diagrams of the clinical trial selection criteria outcomes for Ewing sarcoma (A) and osteosarcoma (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351714&req=5

Figure 1: Flowchart diagrams of the clinical trial selection criteria outcomes for Ewing sarcoma (A) and osteosarcoma (B).
Mentions: A flow-chart indicating the identification of clinical trials for inclusion in the analysis is reported for Ewing sarcoma (Figure 1A) and osteosarcoma (Figure 1B). During the search many reports had to be excluded because no results were published. When we searched the reports using full text, we had to exclude some papers because neither osteosarcoma nor Ewing sarcoma patients were included in these studies. When we combined the results, we identified 42 trials enrolling patients with any histological diagnosis of sarcoma that were eligible for our study, in that they included osteosarcoma and Ewing sarcoma. Of the 42 clinical trials twenty-one were phase I, two were phase I/II and nineteen were phase II trials. We found eight clinical trials which included only Ewing sarcoma patients; of this group two were phase I and six were phase II trials. We identified twenty trials that included only osteosarcoma patients. There were two phase I, sixteen were phase II and two were phase I/II trials. A total of 3,736 patients were included in all the clinical trials, of which 1,263 were Ewing sarcoma and 1,114 were osteosarcoma patients.

Bottom Line: 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 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oncology, Oxford Cancer and Haematology Centre, Churchill Hospital, University of Oxford, Oxford OX3 7LJ, UK. bass.hassan@path.ox.ac.uk.

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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus