Particular cutaneous side effects with etoposide-containing courses: is VP16 or etoposide phosphate responsible?

Abstract

Etoposide is commercially available in France in two different pharmaceutical forms: VP16 and its phosphate ester (etoposide phosphate, EP). EP shows better chemical and physical properties, is said to be less toxic but is five times more expensive than VP16. Some criteria were defined for the use of each form in the Paediatric Oncohaematology Department in Hopital Sud in Rennes. As some particular cutaneous side effects were observed during treatment with etoposide-based course in this department, a retrospective study was initiated. The aims of this work were to determine the side effects (especially cutaneous toxicity), whether the pharmaceutical formulation of etoposide had any influence on the toxicity of the drug, and whether the observed side effects resulted from etoposide alone or from particular antineoplastic drug associations. Five types of etoposide-containing protocols were chosen: NB 97 and NB 99 (neuroblastoma), FRALLE 93 (acute lymphoid leukaemia), LAME 91 (acute myeloid leukaemia), OS 94 (osteosarcoma), Ewing 97 and Euro-Ewing 99 (Ewing sarcoma). The medical files of 36 children (88 EP courses, 25 VP16 courses) included in these protocols were analysed on the basis that if a child showed a side effect during a course, the child had to have recovered from that side effect before the beginning of the next course. Apart from classical side effects (haematological and digestive toxicities etc.), two particular cutaneous side effects were observed: (1) palmar-plantar eruptions and nail inflammations, and (2) irritation of the anal area and anal fissures. Those side effects were observed with three of the studied protocols: NB 97, OS 94 and Ewing sarcoma treatments. No striking differences in toxicity appeared between the two etoposide formulations, but this retrospective study seemed to confirm the appearance of particular cutaneous and anal side effects especially with two associations: (1) etoposide-ifosfamide (OS 94 and Ewing 97), and (2) etoposide-ifosfamide-Adriamycin-vincristine (VIDE course of the Euro-Ewing 99 protocol).