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Randomized Controlled Trial
. 2012 Mar;48(5):703-12.
doi: 10.1016/j.ejca.2011.09.012. Epub 2011 Oct 27.

Presence of chemotherapy-induced toxicity predicts improved survival in patients with localised extremity osteosarcoma treated with doxorubicin and cisplatin: a report from the European Osteosarcoma Intergroup

Anne McTiernan  1 , Rachel C Jinks, Matthew R Sydes, Barbara Uscinska, Jane M Hook, Martine van Glabbeke, Vivien Bramwell, Ian J Lewis, Antonie H M Taminiau, Marianne A Nooij, Pancras C W Hogendoorn, Hans Gelderblom, Jeremy S Whelan
Affiliations
Randomized Controlled Trial

Presence of chemotherapy-induced toxicity predicts improved survival in patients with localised extremity osteosarcoma treated with doxorubicin and cisplatin: a report from the European Osteosarcoma Intergroup

Anne McTiernan et al. Eur J Cancer. 2012 Mar.

Abstract

Aim: Chemotherapy-induced toxicity is an independent prognostic indicator in several cancers. We aimed to determine whether toxicity was related to survival and histological response in high-grade localised extremity osteosarcoma. We undertook a retrospective analysis of patients treated within three consecutive randomised controlled trials (RCTs) of the European Osteosarcoma Intergroup.

Methods: Between 1982 and 2002, 533 patients were randomised to six cycles of doxorubicin 75 mg/m(2) and cisplatin 100 mg/m(2). Toxicity data were collected prospectively and graded according to the World Health Organisation (WHO) criteria. Standard univariate and multivariate models were constructed to examine the relationship between reported toxicity, survival, and histological response.

Results: Five- and 10-year overall survival was 57% (95% confidence interval (CI) 52-61%) and 53% (49-58%), respectively. Grades 3-4 oral mucositis (hazard ratio (HR) 0.51, 95% CI 0.29-0.91), grades 1-2 nausea/vomiting (HR 0.37, 95% CI 0.16-0.85), grades 1-2 thrombocytopenia (HR 0.49, 95% CI 0.27-0.87), good histological response (HR 0.42, 95% CI 0.27-0.65), and distal tumour site (HR 0.45, 95% CI 0.28-0.71) were associated with improved survival in multivariate analysis. The only factors that were independently associated with histological response were older age (odds ratio (OR) 0.18, 95% CI 0.04-0.72) and chondroblastic tumour (OR 0.28, 95% CI 0.10-0.77), both being associated with a significantly lower chance of achieving a good response.

Conclusion: Chemotherapy-induced toxicity predicts survival in patients with localised extremity osteosarcoma. Investigation of the pharmacogenomic mechanisms of constitutional chemosensitivity underlying these observations will present opportunities for personalising treatment and could lead to improved outcomes.

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Figures

Fig. 1
Fig. 1
CONSORT diagram.
Fig. 2
Fig. 2
Overall and progression-free survival.
Fig. 3
Fig. 3
Overall survival, according to chemotherapy related toxicity.
See this image and copyright information in PMC

References

    1. Bacci G., Longhi A., Versari M. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer. 2006;106:1154–1161. - PubMed
    1. Bielack S.S., Kempf-Bielack B., Delling G. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002;20:776–790. - PubMed
    1. Davis A.M., Bell R.S., Goodwin P.J. Prognostic factors in osteosarcoma: a critical review. J Clin Oncol. 1994;12:423–431. - PubMed
    1. Souhami R.L., Craft A.W., Van der Eijken J.W. Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study of the European Osteosarcoma Intergroup. Lancet. 1997;350:911–917. - PubMed
    1. Hauben E.I., Weeden S., Pringle J., Van Marck E.A., Hogendoorn P.C. Does the histological subtype of high-grade central osteosarcoma influence the response to treatment with chemotherapy and does it affect overall survival? A study on 570 patients of two consecutive trials of the European Osteosarcoma Intergroup. Eur J Cancer. 2002;38:1218–1225. - PubMed

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