Gender differences may influence outcomes with vincristine, doxorubicin, and cyclophosphamide (VAC) in the treatment of patients with standard-risk Ewing sarcoma, a recent study published online ahead of print in the European Journal of Cancer has shown.

A previous study called Euro-EWING99-R1 compared the safety and efficacy of VAC with vincristine, doxorubicin, and ifosfamide (VAI) for standard-risk Ewing sarcoma and found that VAC may be able to replace VAI; however, outcomes differed between genders.

Therefore, researchers sought to conduct an exploratory analysis to evaluate the impact of gender on treatment efficacy and toxicity.

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Results showed that event-free survival was not significantly different between the 509 men and 347 women (P=0.33), but VAC was associated with a shorter event-free survival than VAI in males (HR = 1.37; 95% CI: 0.98, 1.90). On the other hand, VAC was associated with a better event-free survival compared with VAI in women (HR = 0.81; 95% CI: 0.53, 1.24).

In regard to safety, researchers found that severe toxicity was more common in women than men. Moreover, 12% of women patients and 4% of men patients switched from VAI to VAC, mostly due to renal toxicity, while only 0.6% and 0.8% of women and men patients, respectively, switched from VAC to VAI.

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The study also demonstrated that women were more likely than men to require a >20% cumulative dose reduction of cyclophosphamide or ifosfamide (P=0.005).

The findings suggest that further studies are warranted to explore the role of gender on VAC/VAI treatment outcomes in patients with Ewing sarcoma.


  1. van den Berg H, Paulussen M, Le Teuff G, et al. Impact of gender on efficacy and acute toxicity of alkylating agent -based chemotherapy in Ewing sarcoma: secondary analysis of the Euro-Ewing99-R1 trial. E J Cancer. 2015. [epub ahead of print]. doi: 10.1016/j.ejca.2015.06.123.