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.


Related in: MedlinePlus

Distribution of the number of trials published that have recruited either osteosarcoma or Ewing sarcoma patients between 1990-2010 (A). The total number of either osteosarcoma or Ewing Sarcoma patients entered in phase I/II trials published between 1990-2010 (B).
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Figure 2: Distribution of the number of trials published that have recruited either osteosarcoma or Ewing sarcoma patients between 1990-2010 (A). The total number of either osteosarcoma or Ewing Sarcoma patients entered in phase I/II trials published between 1990-2010 (B).

Mentions: Tables 1 and 2 show the search results for clinical trials conducted in patients with the wider diagnosis of general sarcoma, and specifically the trials that included either osteosarcoma (Table 3) or Ewing sarcoma patients only (Table 4). Table 1 and 2 are trials testing either chemotherapy or biological treatments, respectively. Analysis of the number of trials conducted which included only osteosarcoma or Ewing sarcoma patients from 1990 to the present, (Figure 2A) it was clear that the number of trials reported for osteosarcoma has been stable since 1995, with approximately five trials in five years. For Ewing sarcoma there has been an increase in the number of trials published, with the no early phase trials reported between 1990 and 1999, an increasing number of trials in the period 2000-2005 and even more between 2006-2010.


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)

Distribution of the number of trials published that have recruited either osteosarcoma or Ewing sarcoma patients between 1990-2010 (A). The total number of either osteosarcoma or Ewing Sarcoma patients entered in phase I/II trials published between 1990-2010 (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Distribution of the number of trials published that have recruited either osteosarcoma or Ewing sarcoma patients between 1990-2010 (A). The total number of either osteosarcoma or Ewing Sarcoma patients entered in phase I/II trials published between 1990-2010 (B).
Mentions: Tables 1 and 2 show the search results for clinical trials conducted in patients with the wider diagnosis of general sarcoma, and specifically the trials that included either osteosarcoma (Table 3) or Ewing sarcoma patients only (Table 4). Table 1 and 2 are trials testing either chemotherapy or biological treatments, respectively. Analysis of the number of trials conducted which included only osteosarcoma or Ewing sarcoma patients from 1990 to the present, (Figure 2A) it was clear that the number of trials reported for osteosarcoma has been stable since 1995, with approximately five trials in five years. For Ewing sarcoma there has been an increase in the number of trials published, with the no early phase trials reported between 1990 and 1999, an increasing number of trials in the period 2000-2005 and even more between 2006-2010.

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