Journal ArticleDOI
Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study.
Sant P. Chawla,Robert M. Henshaw,Leanne L. Seeger,Edwin Choy,Jean-Yves Blay,Stefano Ferrari,Judith R. Kroep,Robert J. Grimer,Peter Reichardt,Piotr Rutkowski,Scott M. Schuetze,Keith M. Skubitz,Arthur P. Staddon,David Thomas,Yi Qian,Ira Jacobs +15 more
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Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB and represents a new treatment option for patients with the rare giant cell tumour of bone.Abstract:
Summary Background Giant cell tumour of bone (GCTB) is a very rare, aggressive, and progressive osteolytic tumour for which no standard medicinal treatment or chemotherapy exists. We report interim safety and efficacy results from a phase 2 study of denosumab in patients with GCTB. Methods We did an international, open-label, parallel-group, phase 2 trial of patients with histologically confirmed GCTB and radiographically measurable active disease. Eligible patients were adults or skeletally mature adolescents with radiographic evidence of at least one mature long bone who were at least 12 years old and weighed at least 45 kg. We divided patients into three cohorts—those with surgically unsalvageable GCTB (cohort 1), those with salvageable GCTB whose surgery was associated with severe morbidity (cohort 2), and those who transferred from a previous study of denosumab for GCTB (cohort 3). Patients in cohorts 1 and 2 received 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle; those in cohort 3 continued the regimen from the previous study. Investigator-determined disease status and clinical benefit were assessed every 4 weeks. Our primary endpoint was the safety profile of denosumab in terms of adverse events and laboratory abnormalities. Prespecified secondary endpoints were time to disease progression in cohort 1 and the proportion of patients without any surgery at 6 months in cohort 2. Safety analyses included all patients who received at least one dose of denosumab. Efficacy analyses included all eligible patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, identifier NCT00680992. Findings 282 patients, including ten adolescents, were included between Sept 9, 2008, and March 25, 2011. Of the 281 patients analysable for safety, three (1%) had osteonecrosis of the jaw and 15 (5%) hypocalcaemia. The most common grade 3–4 adverse events were hypophosphataemia, which occurred in nine (3%) patients, and anaemia, back pain, and pain in extremities, each of which occurred in three patients (1%). Serious adverse events were reported in 25 (9%) patients. No treatment-related deaths were reported. On the basis of investigators' assessment of disease status, 163 of 169 (96%) analysable patients in cohort 1 had no disease progression after median follow-up of 13 months (IQR 5·8–21·0). In cohort 2, 74 of 100 (74%) analysable patients had no surgery and 16 of 26 (62%) patients who had surgery underwent a less morbid procedure than planned. Median follow-up in cohort 2 was 9·2 months (IQR 4·2–12·9). Interpretation Adverse events were consistent with the known safety profile of denosumab. Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB. Denosumab represents a new treatment option for patients with GCTB. Funding Amgen.read more
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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines
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Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Paolo G. Casali,J.-Y. Blay +1 more
TL;DR: The following recommendations apply to adult-type soft tissue sarcomas arising from limbs and superficial trunk and Extraskeletal Ewing sarcoma, which is excluded from this chapter.
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Bone Sarcomas : ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (vol 25, pg iii113, 2014)
J.-Y. Blay,Alexia Bertuzzi,Stefan S. Bielack,Bodil Bjerkehagen,S. Bonvalot,Ioannis Boukovinas,Paolo Bruzzi,A. P. Dei Tos,P. Dileo,Mikael Eriksson,A. Fedenko,Andrea C. Ferrari,Silvia Ferrari,Hans Gelderblom,R. J. Grimer,Alessandro Gronchi,R. L. Haas,Kirsten Sundby Hall,Peter Hohenberger,Rolf-Dieter Issels,Heikki Joensuu,Ian Judson,A. Le Cesne,S. Litiere,J. Martin-Broto,Ofer Merimsky,Michael Montemurro,Carlo Morosi,P. Picci,I.L. Ray-Coquard,Peter Reichardt,Piotr Rutkowski,Marcus Schlemmer,Silvia Stacchiotti,Valter Torri,Annalisa Trama,F. van Coevorden,Daniel Vanel,Eva Wardelmann,Paolo G. Casali +39 more
TL;DR: Osteosarcoma and Ewing sarcoma have a relatively high incidence in the second decade of life, while chondrosarcomas are more common in older age groups, and chordomas are rare; arising with an incidence of ∼0.5/ million population per year.
Journal ArticleDOI
Bone sarcomas: ESMO-PaedCan-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up
Paolo G. Casali,Stefan S. Bielack,N. Abecassis,Hannu T. Aro,Sebastian Bauer,R. Biagini,Sylvie Bonvalot,Ioannis Boukovinas,Judith V.M.G. Bovée,Bernadette Brennan,Thomas Brodowicz,Javier Martin Broto,Laurence Brugières,Angela Buonadonna,E. de Álava,A. P. Dei Tos,X.G. del Muro,Palma Dileo,Catharina Dhooge,Mikael Eriksson,Franca Fagioli,Alexander Fedenko,Virginia Ferraresi,Andrea Ferrari,S. Ferrari,A.M. Frezza,Nathalie Gaspar,Silvia Gasperoni,Hans Gelderblom,Thierry Gil,Giovanni Grignani,Alessandro Gronchi,Rick L. Haas,B. Hassan,Stefanie Hecker-Nolting,Peter Hohenberger,Rolf D. Issels,Heikki Joensuu,Robin L. Jones,Ian Judson,Paul C Jutte,Suzanne E. J. Kaal,Leo Kager,Bernd Kasper,Katerina Kopeckova,D.A. Krakorova,Ruth Ladenstein,A. Le Cesne,Iwona Lugowska,Ofer Merimsky,Michael Montemurro,Bruce Morland,Maria Abbondanza Pantaleo,R. Piana,P. Picci,S. Piperno-Neumann,Antonio López Pousa,Peter Reichardt,M.H. Robinson,Piotr Rutkowski,Akmal Safwat,Patrick Schöffski,Stefan Sleijfer,Silvia Stacchiotti,Sandra J. Strauss,K. Sundby Hall,M. Unk,F. van Coevorden,W.T.A. van der Graaf,W.T.A. van der Graaf,W.T.A. van der Graaf,Jeremy Whelan,Eva Wardelmann,Olga Zaikova,Jean-Yves Blay +74 more
TL;DR: Primary bone tumours are rare, accounting for < 0.2% of malignant neoplasms registered in the EUROCARE (European Cancer Registry based study on survival and care of cancer patients) database, and different bone tumour subtypes have distinct patterns of incidence.
Journal ArticleDOI
UK guidelines for the management of bone sarcomas
Craig Gerrand,Nicholas A. Athanasou,Bernadette Brennan,Robert J. Grimer,Ian Judson,Bruce Morland,David Peake,Beatrice Seddon,Jeremy Whelan +8 more
TL;DR: This document is an update of the British Sarcoma Group guidelines and recommends that patients with clinico-radiological findings suggestive of a primary bone tumour at any site in the skeleton should be referred to a specialist centre and managed by a fully accredited bone sarcoma multidisciplinary team.
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