Journal
ANNALS OF ONCOLOGY
Volume 23, Issue 6, Pages 1607-1616Publisher
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdr491
Keywords
adolescents; chemotherapy; osteosarcoma; randomised controlled trial
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Funding
- UK Medical Research Council
- National Institute of Health Research Comprehensive Biomedical Research Centre
- MRC [MC_U122861384] Funding Source: UKRI
- Medical Research Council [MC_U122861384] Funding Source: researchfish
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Background: Neoadjuvant chemotherapy improves outcome in osteosarcoma. Determination of optimum regimens for survival, toxicity and prognostic factors requires randomised controlled trials to be conducted. Patients and methods: 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/m(2) and cisplatin 100 mg/m(2). 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. Results: 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. Conclusions: 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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