RESEARCH SUPPORT, NON-U.S. GOV'T
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Oral etoposide for recurrent/progressive sarcomas of childhood.

BACKGROUND: Etoposide (VP-16) is a topoisomerase II inhibitor that is effective in a broad spectrum of pediatric and adult malignancies. Chronic, low-dose, oral VP-16 has also been shown to be active in some recurrent malignancies mostly in adults. The aim of this prospective, single institution study is to assess the efficacy and toxicity of oral VP-16 in children with progressive or recurrent (P/R) sarcomas.

PROCEDURE: Twenty-one children (10 girls and 11 boys) with R/P sarcomas and a median age of 11 years (range 3-16 years) were enrolled in this study. The diagnosis was Ewing sarcoma family tumor (ESFT) in seven, osteosarcoma in eight, rhabdomyosarcoma in four, clear cell sarcoma of soft tissue in one, fibrosarcoma in one patient. Oral VP-16 was administered at a dose of 50 mg/m(2)/daily for 20 days. The next course was initiated after a 10 day rest. Response to oral VP-16 was assessed after two courses.

RESULTS: There was an objective response (one complete response [CR], two partial responses [PR]) in three patients (14%) by two courses of oral VP-16 alone. One of these patients with PR achieved CR by the use of radiotherapy (RT) and further oral VP-16. Two more patients (9.5%) achieved CR by RT and oral VP-16. Eight (38%) patients had disease stabilization for 2-15 months. Two patients (9.5%) are long-term survivors. They are alive with no evidence of disease (NED) 79 and 94 months from time of relapse/progressive disease (PD). A patient developed acute myeloid leukemia and died. There was no major acute toxicity related to oral VP-16 in a total of 126 courses.

CONCLUSIONS: Oral VP-16 therapy is simple, relatively nontoxic, and does not necessitate hospitalization. The cure rate is small. Given the risk of second malignancy, especially in children with previous exposure to topoisomerase II inhibitors and alkylating agents, this regimen may be used as a palliative treatment or in patients with poor prognosis.

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