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


METHODS
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.
Le Deley
Marie-Cécile
MC
Biostatistics and Epidemiology Unit, Institut Gustave-Roussy, 94805 Villejuif, France. le_deley@igr.fr
Vassal
Gilles
G
Taïbi
Ahmed
A
Shamsaldin
Akthar
A
Leblanc
Thierry
T
Hartmann
Olivier
O
D000293:Adolescent; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007223:Infant; D007938:Leukemia / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000453:epidemiology; D010166:Palliative Care; D015996:Survival Rate
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide