High cumulative rate of secondary leukemia after continuous etoposide treatment for solid tumors in children and young adults

Abstract

Background: In a national pediatric case-control study, we observed a very high relative risk of leukemia in patients who had received continuous etoposide (CE) over 6 months or more, but we could not estimate the absolute risk. The purpose of the present study was to estimate this absolute risk after CE.

Procedures: We report a study of 18 patients with refractory or recurrent tumors who received CE over 6 months or more between 1995 and 1997. It was administered either 3 days a week for 3/4 weeks ("3 x 3", 14 patients) or 7 days a week for 3/4 weeks ("7 x 3", four patients).

Results: Five patients developed secondary leukemia 10-25 months after the initiation of CE. All the others died of their first tumor. The cumulative incidence of leukemia at 30 months was 28% (95% CI, 10%-53%). A chromosome 11q23 rearrangement was found in 3/5 cases. All four patients who received the "7 x 3" CE schedule developed leukemia compared to 1/14 treated with the "3 x 3" CE schedule (P = 0.002).

Conclusions: Given its efficacy, CE may still have a place as a palliative treatment. However, the risk of leukemia must be borne in mind when considering its use in patients with a better prognosis.