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      Clinical Activity of Pazopanib in Metastatic Extraosseous Ewing Sarcoma

      case-report

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          Abstract

          We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371). This national multi-institutional study is ongoing.

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          Prognostic factors in Ewing's tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing's Sarcoma Study Group.

          S Cotterill, S. Ahrens, M. Paulussen … (2000)
          To further elaborate on prognostic factors for Ewing's sarcoma of bone and to document improvements in relapse-free survival (RFS) and trends in local therapy over the study period (1977 to 1993). A retrospective analysis was performed on a combined Gesellschaft Für Pädiatrische Onkologie und Hämatologie/Cooperative Ewing Sarcoma Study and United Kingdom Children's Cancer Study Group/Medical Research Council data set of 975 patients registered with the respective trial offices before the current collaborative European Intergroup Cooperative Ewing's Sarcoma Study trial. Both groups independently undertook studies with similar chemotherapy during the period. The key adverse prognostic factor is metastases at diagnosis (5-year RFS, 22% of patients with metastases at diagnosis v 55% of patients without metastases at diagnosis; P: or = 15 years), and period of diagnosis had significant influence on RFS (all P: <.005). RFS was superior in the period after 1985 compared with the period before 1985 for nonmetastatic patients (45% v 60%, respectively; P: <.0001) and for metastatic patients (16% v 30%, respectively; P: =.016). Patients who relapsed within 2 years of diagnosis had a less favorable prognosis than patients who relapsed later (5-year survival after relapse, 4% v 23%, respectively; P: <. 0001). There were other changes over the period; in particular, radiotherapy or amputation were more common in the period before 1986, whereas endoprosthetic surgery was widely used in the later period. Survival and RFS improved over the period. Prognostic factors are metastases at diagnosis, primary site, and age.
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            Clinical features and outcomes in patients with extraskeletal Ewing sarcoma.

            Mark A Applebaum, John Neuhaus, S. Dubois … (2011)
            Ewing sarcoma can arise in either bone or soft tissue. The purpose of this study was to investigate whether patient characteristics, treatment strategies, and outcomes differ between skeletal Ewing sarcoma and extraskeletal Ewing sarcoma (EES). Patients <40 years of age with Ewing sarcoma or peripheral primitive neuroectodermal tumor reported to the United States Surveillance, Epidemiology, and End Results Program database from 1973 to 2007 were evaluated based on skeletal (n = 1519) versus extraskeletal (n = 683) site of origin. Patient characteristics were compared using Fisher exact tests. Overall survival was estimated via the Kaplan-Meier method and compared using log-rank tests and Cox proportional hazard models. Patients with EES had a higher mean age (19.5 vs 16.3 years; P < .001) and were less likely to be male (53.4% vs 63.3%; P < .001) or white (84.8% vs 92.5%; P < .001) compared with patients with skeletal tumors. Extraskeletal tumors were more likely to arise in axial locations (72.9% vs 54.2%; P = .001) but were less likely to arise specifically in the pelvis (19.8% vs 26.6%; P < .001). Metastatic status or tumor size did not differ by group. Five-year overall survival was superior for localized EES compared with localized skeletal tumors (69.7% vs 62.6%; P = .02). The hazard ratio for death in patients with localized skeletal tumors compared with localized EES was 2.36 (95% confidence interval, 1.61-3.44) beyond 24 months from initial diagnosis. Patient characteristics and outcomes differ among patients with EES compared with patients with skeletal Ewing sarcoma. These findings may have important implications for patient care. Copyright © 2011 American Cancer Society.
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              Pazopanib: Clinical development of a potent anti-angiogenic drug.

              Fabio Schutz, Toni K. Choueiri, Cora N Sternberg (2011)
              Pazopanib is an oral, multi-targeted, tyrosine kinase inhibitor (TKI) that binds to the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and several other key proteins responsible for angiogenesis, tumor growth and cell survival. Pazopanib exhibited in vivo and in vitro activity against tumor growth and, in early clinical trials, was well tolerated with the main side effects being hypertension, fatigue and gastrointestinal disorders. Pazopanib showed clinical activity in several tumors including renal cell cancer (RCC), breast cancer, soft tissue sarcoma, thyroid cancer, hepatocellular cancer and cervical cancer. A phase III clinical trial in metastatic RCC patients showed a significant improvement in progression-free survival, leading to its approval in the US. In metastatic breast cancer, the combination of pazopanib with lapatinib was more effective than lapatinib alone. At the time of the current publication, pazopanib is being evaluated in more than 35 phase II and III trials. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Rare Tumors
                Journal ID (iso-abbrev): Rare Tumors
                Journal ID (publisher-id): RT
                Title: Rare Tumors
                Publisher: PAGEPress Publications, Pavia, Italy
                ISSN (Print): 2036-3605
                ISSN (Electronic): 2036-3613
                Publication date (Electronic): 21 May 2015
                Publication date Collection: 05 May 2015
                Volume: 7
                Issue: 2
                Electronic Location Identifier: 5992
                Affiliations
                [1 ]Mayo Clinic , Jacksonville, FL, USA
                [2 ]Mayo Clinic , Rochester, MN, USA
                [3 ]3Aurora Healthcare , Milwaukee, WI, USA
                [4 ]4University of Florida , Jacksonville, FL, USA
                [5 ]Royal Marsden Hospital , London, UK
                [6 ]Mercy Medical Center , Janesville, WI, USA
                [7 ]University of Wisconsin , Madison, WI, USA
                [8 ]University of Miami , FL, USA
                [9 ]Mount Sinai Medical Center , New York, NY, USA
                Author notes
                Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, USA. +1.904.953.7292 - +1.904.953.6801. farfuso@ 123456unime.it

                Contributions: the authors contributed equally.

                Conflict of interest: the authors declare no potential conflict of interest.

                Article
                DOI: 10.4081/rt.2015.5992
                PMC ID: 4508650
                PubMed ID: 26266019
                SO-VID: 3cbb0417-bf37-4829-861b-0b113b665423
                Copyright © ©Copyright S. Attia et al.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 07 May 2015
                Date accepted : 13 May 2015
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 11, Pages: 3
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: ewing,sarcoma,pazopanib
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: ewing, sarcoma, pazopanib

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