PURPOSE: The three-drug combination of melphalan (M), etoposide (E), and carboplatin (C) followed by autologous stem-cell (ASC) rescue has been evaluated prospectively by the French Society of Pediatric Oncology (SFOP) in pediatric high-risk recurrent (HRR) Wilms' tumor (WT) patients 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 regimen and have been studied separately. The regimen consisted of M 180 mg/m2 for 1 day, E 200 mg/m2/d for 5 days, and C at a daily targeted area under the concentration-time curve (AUC) of 4 mg x min/mL for 5 days. ASCs were reinfused 48 hours after M. RESULTS: Twelve of 28 assessable patients with HRR WT are still in continuous CR at a median of 48.5 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 patients relapsed at a median of 8.5 months (range, 3 to 53) after consolidation. Toxicity data are available in 31 grafted patients. Grade III and IV toxicities included hematologic side effects (n=31), hemorrhage (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 define 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 chemotherapy (HDCT) is performed as early as the second CR or partial response (PR). Novel therapeutic approaches with innovative preparative regimens are warranted for the remaining high-risk patients.
PURPOSE: The three-drug combination of melphalan (M), etoposide (E), and carboplatin (C) followed by autologous stem-cell (ASC) rescue has been evaluated prospectively by the French Society of Pediatric Oncology (SFOP) in pediatric high-risk recurrent (HRR) Wilms' tumor (WT) patients 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 regimen and have been studied separately. The regimen consisted of M 180 mg/m2 for 1 day, E 200 mg/m2/d for 5 days, and C at a daily targeted area under the concentration-time curve (AUC) of 4 mg x min/mL for 5 days. ASCs were reinfused 48 hours after M. RESULTS: Twelve of 28 assessable patients with HRR WT are still in continuous CR at a median of 48.5 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 patients relapsed at a median of 8.5 months (range, 3 to 53) after consolidation. Toxicity data are available in 31 grafted patients. Grade III and IV toxicities included hematologic side effects (n=31), hemorrhage (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 define 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 chemotherapy (HDCT) is performed as early as the second CR or partial response (PR). Novel therapeutic approaches with innovative preparative regimens are warranted for the remaining high-risk patients.
Authors: Steven Allen; Matthew W Wilson; Amy Watkins; Catherine Billups; Ibrahim Qaddoumi; Barrett H Haik; Carlos Rodriguez-Galindo Journal: Pediatr Blood Cancer Date: 2010-07-15 Impact factor: 3.167
Authors: Conrad V Fernandez; Elizabeth A Mullen; Yueh-Yun Chi; Peter F Ehrlich; Elizabeth J Perlman; John A Kalapurakal; Geetika Khanna; Arnold C Paulino; Thomas E Hamilton; Kenneth W Gow; Zelig Tochner; Fredric A Hoffer; Janice S Withycombe; Robert C Shamberger; Yeonil Kim; James I Geller; James R Anderson; Paul E Grundy; Jeffrey S Dome Journal: J Clin Oncol Date: 2017-12-06 Impact factor: 44.544
Authors: Diana S Osorio; Ira J Dunkel; Kelly Ann Cervone; Rakesh K Goyal; K M Steve Lo; Jonathan L Finlay; Sharon L Gardner Journal: Pediatr Blood Cancer Date: 2017-09-14 Impact factor: 3.167
Authors: Jeffrey S Dome; Norbert Graf; James I Geller; Conrad V Fernandez; Elizabeth A Mullen; Filippo Spreafico; Marry Van den Heuvel-Eibrink; Kathy Pritchard-Jones Journal: J Clin Oncol Date: 2015-08-24 Impact factor: 44.544
Authors: Saskia L Gooskens; Norbert Graf; Rhoikos Furtwängler; Filippo Spreafico; Christophe Bergeron; Gema L Ramírez-Villar; Jan Godzinski; Christian Rübe; Geert O Janssens; Gordan M Vujanic; Ivo Leuschner; Aurore Coulomb-L'Hermine; Anne M Smets; Beatriz de Camargo; Sara Stoneham; Harm van Tinteren; Kathy Pritchard-Jones; Marry M van den Heuvel-Eibrink Journal: Nat Rev Urol Date: 2018-02-27 Impact factor: 14.432
Authors: S L Gooskens; R Furtwängler; F Spreafico; H van Tinteren; J de Kraker; G M Vujanic; I Leuschner; A Coulomb-L'Herminé; J Godzinski; G Schleiermacher; S Stoneham; C Bergeron; K Pritchard-Jones; N Graf; M M van den Heuvel-Eibrink Journal: Br J Cancer Date: 2014-06-17 Impact factor: 7.640