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. 2012 Jun;23(6):1607-16.
doi: 10.1093/annonc/mdr491. Epub 2011 Oct 19.

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

J S Whelan  1 , R C Jinks, A McTiernan, M R Sydes, J M Hook, L Trani, B Uscinska, V Bramwell, I J Lewis, M A Nooij, M van Glabbeke, R J Grimer, P C W Hogendoorn, A H M Taminiau, H Gelderblom
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Survival from high-grade localised extremity osteosarcoma: combined results and prognostic factors from three European Osteosarcoma Intergroup randomised controlled trials

J S Whelan et al. Ann Oncol. 2012 Jun.

Abstract

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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Figures

Figure 1.
Figure 1.
Kaplan–Meier plots for (A) overall survival and (B) progression-free survival (PFS) by trial and (C) overall survival and (D) PFS by treatment arm. D, doxorubicin; C, cisplatin; HDMTx, high-dose methotrexate; G-CSF, granulocyte colony-stimulating factor.
Figure 2.
Figure 2.
Kaplan–Meier plots for (A) overall survival and (B) progression-free survival by treatment completion. Treatment complete: all protocol-specified cycles of chemotherapy given and treatment not complete: any other number of cycles. Patients who stopped protocol treatment due to progression of disease were excluded from this analysis. Reasons for non-completion were toxicity, patient choice and ‘other’.
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