Survival from high-grade localised extremity osteosarcoma: combined results and prognostic factors from three European Osteosarcoma Intergroup randomised controlled trials

Neoadjuvant chemotherapy improves outcome in osteosarcoma. Determination of optimum regimens for survival, toxicity and prognostic factors requires randomised controlled trials to be conducted. Between 1983 and 2002, the European Osteosarcoma Intergroup recruited 1067 patients with localised extremi...

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Bibliographic Details
Published in:	Annals of oncology Vol. 23; no. 6; pp. 1607 - 1616
Main Authors:	Whelan, J.S., Jinks, R.C., McTiernan, A., Sydes, M.R., Hook, J.M., Trani, L., Uscinska, B., Bramwell, V., Lewis, I.J., Nooij, M.A., van Glabbeke, M., Grimer, R.J., Hogendoorn, P.C.W., Taminiau, A.H.M., Gelderblom, H.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 01-06-2012 Oxford University Press
Subjects:	Adolescent adolescents Adult Antineoplastic agents Antineoplastic Combined Chemotherapy Protocols - therapeutic use Arm Bones - pathology Biological and medical sciences Bone Neoplasms - drug therapy Bone Neoplasms - mortality Bone Neoplasms - pathology chemotherapy Child Diseases of the osteoarticular system Female Humans Kaplan-Meier Estimate Leg Bones - pathology Male Medical sciences Multivariate Analysis Neoplasm Grading Neoplasm Recurrence, Local Original osteosarcoma Osteosarcoma - drug therapy Osteosarcoma - mortality Osteosarcoma - pathology Pharmacology. Drug treatments Proportional Hazards Models randomised controlled trial Randomized Controlled Trials as Topic Retrospective Studies Survival Treatment Outcome Tumors of striated muscle and skeleton Young Adult Europe randomised controlled trial adolescents chemotherapy osteosarcoma Human Prognosis Sarcoma Diseases of the osteoarticular system Malignant tumor Survival Randomized controlled trial High grade Osteoarticular system Chemotherapy Treatment Osteosarcoma Limb Adolescent Bone Cancer High malignancy
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Summary:	Neoadjuvant chemotherapy improves outcome in osteosarcoma. Determination of optimum regimens for survival, toxicity and prognostic factors requires randomised controlled trials to be conducted. Between 1983 and 2002, the European Osteosarcoma Intergroup recruited 1067 patients with localised extremity osteosarcoma to three randomised controlled trials. Standard treatment in each was doxorubicin 75 mg/m2 and cisplatin 100 mg/m2. Comparators were addition of methotrexate (BO02/80831), a multidrug regimen (BO03/80861) and a dose-intense schedule (BO06/80931). Standard survival analysis methods were used to identify prognostic factors, temporal and other influences on outcome. Five- and 10-year survival were 56% (95% confidence interval 53% to 59%) and 52%, respectively (49% to 55%), with no difference between trials or treatment arms. Median follow-up was 9.4 years. Age range was 3–40 years (median 15). Limb salvage was achieved in 69%. Five hundred and thirty-three patients received the standard arm, 79% completing treatment. Good histological response to preoperative chemotherapy, distal tumour location (all sites other than proximal humerus/femur) and female gender were associated with improved survival. Localised osteosarcoma will be cured in 50% of patients with cisplatin and doxorubicin. Large randomised trials can be conducted in this rare cancer. Failure to improve survival over 20 years argues for concerted collaborative international efforts to identify and rapidly test new treatments.
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ISSN:	0923-7534 1569-8041
DOI:	10.1093/annonc/mdr491