HIGH-DOSE MELPHALAN, ETOPOSIDE, AND CARBOPLATIN FOLLOWED BY AUTOLOGOUS STEM-CELL RESCUE IN PEDIATRIC HIGH-RISK RECURRENT WILMS-TUMOR - A FRENCH-SOCIETY-OF-PEDIATRIC-ONCOLOGY STUDY

Purpose: The three-drug combination of melphalan (M), etoposide (E), a nd carboplatin (C) followed by autologous stem-cell (ASC) rescue has b een evaluated prospectively by the French Society of Pediatric Oncolog y (SFOP) in pediatric high-risk recurrent (HRR) Wilms' tumor (WT) pati ents with chemotherapy-responsive disease. Patients and Methods: From October 1988 to October 1994, 29 patients with HRR WT were treated in nine SFOP centers. Two additional patients with stage IV anaplastic WT were consolidated in first complete response (CR) with the same regim en and have been studied separately. The regimen consisted of M 180 mg /m(2) for 1 day, E 200 mg/m(2)/d for 5 days, and C at a daily targeted area under the concentration-time curve (AUC) of 4 mg. min/mL for 5 d ays. ASCs were reinfused 48 hours after M. Results: Twelve of 28 asses sable patients with HRR WT are still in continuous CR at a median of 8 .5 months (range, 36 to 96) after consolidation. Disease-free survival (DFS) and overall survival (OS) estimated by the Kaplan-Meier method at 3 years were 50% +/- 17% and 60% +/- 18%, respectively. Sixteen pat ients relapsed at a median of 48.5 months (range, 3 to 53) after conso lidation. Toxicity data are available in 31 grafted patients. Grade II I and IV toxicities included hematologic side effects (n = 3l),hemorrh age(n = 8),mucositis(n = 24), diarrhea (n = 12), renal disorders (n = 8), and pneumonitis(n = 3). Conclusion: The adverse prognostic factors (APF) used to select patients for this dose-intensive chemotherapy de fine children with very-poor-risk recurrent WT. Despite high treatment -related toxicity, about half of these patients remain disease-free at 3 years. patient outcome is statistically better when high-dose chemo therapy (HDCT) is performed as early as the second CR or partial respo nse (PR). Novel therapeutic approaches with innovative preparative reg imens are warranted for the remaining high-risk patients. (C) 1998 by American Society of Clinical Oncology.