5 research outputs found

    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

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    <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

    Etoposide and carbo-or cisplatin combination therapy in refractory or relapsed Ewing sarcoma: a large retrospective study

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    Patients with Ewing sarcoma (EWS) who develop refractory or relapsed disease have limited treatment options. In some sarcoma centres in Europe the combination of etoposide with carbo- or cisplatin is being used for these patients, however, there are no published data available yet. Here we investigated the outcome of the combination treatment for patients with advanced Ewing sarcoma in progression after standard treatment. All patients diagnosed with EWS between 1980 and 2012 in one of six major sarcoma centres in Europe and treated with either carboplatin and etoposide or cisplatin and etoposide were included and data were retrospectively collected for analysis. A total of 107 patients enrolled in this study of which 61 received the combination of etoposide and carboplatin and 46 received etoposide and cisplatin. The median overall survival (OS) was 23 months for both patient groups and the 5-year OS was 24.5% for the patients who received carboplatin and etoposide and 20% for those who received cisplatin and etoposide. The progression free survival was better in patients treated with the combination of carboplatin and etoposide (14.5 vs. 6.3 months P = 0.023). This is a retrospective study on the combination treatment of etoposide and carbo- or cisplatin in refractory Ewing sarcoma. The results justify exploring the combination in a prospective study with relapsed patient

    Outcome of advanced, unresectable conventional central chondrosarcoma

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    Abstract BACKGROUND: For patients who have chondrosarcoma with unresectable disease, because of tumor location, tumor size, or extensive metastatic disease, treatment options are very limited because of their relative resistance to radiotherapy and chemotherapy. The overall survival of this patient population is poor; however, specific studies are lacking, and large series have not been published. Therefore, the authors conducted this retrospective, 2-center study to gain insight into the outcome of patients with advanced, unresectable, conventional central chondrosarcoma. METHODS: All patients with unresectable conventional central chondrosarcoma who were diagnosed between January 1, 1980 and December 31, 2011 in 2 major European bone sarcoma centers (Rizzoli Institute, Bologna, Italy and Leiden University Medical Center, Leiden, the Netherlands) were selected. Relevant information was collected from the medical records at both centers. RESULTS: In total, 171 patients met the selection criteria. The overall survival rate for all patients was 48% at 1 year, 24% at 2 years, 12% at 3 years, 6% at 4 years, and 2% at 5 years. Patients with unresectable, locally advanced disease without distant metastases had a significantly better survival than patients with metastatic disease (P\u2009=\u2009.0014). Systemic treatment, consisting of either doxorubicin-based chemotherapy or the noncytotoxic drugs imatinib and sirolimus, improved survival significantly compared with no treatment (P\u2009=\u2009.0487). For patients who had locally advanced disease without metastases, radiotherapy was associated with a survival benefit (P\u2009=\u2009.0032). CONCLUSIONS: This study provides a standard for overall survival rates after a diagnosis of unresectable conventional central chondrosarcoma. Systemic treatment and radiotherapy may improve survival, although selection bias because of the retrospective nature of this study may have influenced the outcome. The poor survival underlines the need for new therapeutic options for this patient population. Cancer 2014. \ua9 2014 American Cancer Society. \ua9 2014 American Cancer Society

    Outcome of advanced, unresectable conventional central chondrosarcoma

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    Abstract BACKGROUND: For patients who have chondrosarcoma with unresectable disease, because of tumor location, tumor size, or extensive metastatic disease, treatment options are very limited because of their relative resistance to radiotherapy and chemotherapy. The overall survival of this patient population is poor; however, specific studies are lacking, and large series have not been published. Therefore, the authors conducted this retrospective, 2-center study to gain insight into the outcome of patients with advanced, unresectable, conventional central chondrosarcoma. METHODS: All patients with unresectable conventional central chondrosarcoma who were diagnosed between January 1, 1980 and December 31, 2011 in 2 major European bone sarcoma centers (Rizzoli Institute, Bologna, Italy and Leiden University Medical Center, Leiden, the Netherlands) were selected. Relevant information was collected from the medical records at both centers. RESULTS: In total, 171 patients met the selection criteria. The overall survival rate for all patients was 48% at 1 year, 24% at 2 years, 12% at 3 years, 6% at 4 years, and 2% at 5 years. Patients with unresectable, locally advanced disease without distant metastases had a significantly better survival than patients with metastatic disease (P\u2009=\u2009.0014). Systemic treatment, consisting of either doxorubicin-based chemotherapy or the noncytotoxic drugs imatinib and sirolimus, improved survival significantly compared with no treatment (P\u2009=\u2009.0487). For patients who had locally advanced disease without metastases, radiotherapy was associated with a survival benefit (P\u2009=\u2009.0032). CONCLUSIONS: This study provides a standard for overall survival rates after a diagnosis of unresectable conventional central chondrosarcoma. Systemic treatment and radiotherapy may improve survival, although selection bias because of the retrospective nature of this study may have influenced the outcome. The poor survival underlines the need for new therapeutic options for this patient population. Cancer 2014. \ua9 2014 American Cancer Society. \ua9 2014 American Cancer Society
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