BACKGROUND: After randomized trials in the 1980s, doxorubicin (DOX) was added to dactinomycin plus vincristine as standard chemotherapy for patients who had Stage III Wilms tumor (WT) of favorable histology (FH). Double-agent chemotherapy was retained for patients with Stage II disease. In this study, the authors reevaluated the efficacy of DOX using extended follow-up and additional patients. METHODS: The relative risks (RR) (DOX vs. no DOX) of disease recurrence and mortality were estimated for patients with Stage II-III/FH WT who were enrolled in the third and fourth National Wilms Tumor Studies (NWTS-3 and NWTS-4). The risk of congestive heart failure (CHF) was estimated for all patients who received DOX. RESULTS: No statistically significant effects of DOX were found for patients with Stage II tumors. For patients with Stage III tumors, the 8 year recurrence-free survival (RFS) and overall survival (OS) rates for randomized patients on NWTS-3 were 84% and 89%, respectively, for patients who received DOX (n = 130) and 74% and 83%, respectively, for patients who did not receive DOX (n = 118). Including all patients with Stage III disease who received DOX (n = 678) and did not receive DOX (n = 138), the RRs of recurrence were 0.47 (P = 0.007) and 0.40 (P = 0.011), and local recurrence respectively, after adjustment for radiation therapy (RT) dose, whereas the RR of mortality adjusted for RT and study was 0.68 (P = 0.17). The 20-year risk of CHF after primary DOX treatment on NWTS-3 and NWTS-4 was 1.2%. CONCLUSIONS: The inclusion of data from nonrandomized patients yielded estimates of DOX treatment effects for Stage III/FH WT that were stronger, albeit more susceptible to bias, than reported previously. Despite a lower reported risk of CHF, conclusive evidence that frontline therapy with DOX definitively improves survival remains elusive. Copyright 2004 American Cancer Society.
RCT Entities:
BACKGROUND: After randomized trials in the 1980s, doxorubicin (DOX) was added to dactinomycin plus vincristine as standard chemotherapy for patients who had Stage III Wilms tumor (WT) of favorable histology (FH). Double-agent chemotherapy was retained for patients with Stage II disease. In this study, the authors reevaluated the efficacy of DOX using extended follow-up and additional patients. METHODS: The relative risks (RR) (DOX vs. no DOX) of disease recurrence and mortality were estimated for patients with Stage II-III/FH WT who were enrolled in the third and fourth National Wilms Tumor Studies (NWTS-3 and NWTS-4). The risk of congestive heart failure (CHF) was estimated for all patients who received DOX. RESULTS: No statistically significant effects of DOX were found for patients with Stage II tumors. For patients with Stage III tumors, the 8 year recurrence-free survival (RFS) and overall survival (OS) rates for randomized patients on NWTS-3 were 84% and 89%, respectively, for patients who received DOX (n = 130) and 74% and 83%, respectively, for patients who did not receive DOX (n = 118). Including all patients with Stage III disease who received DOX (n = 678) and did not receive DOX (n = 138), the RRs of recurrence were 0.47 (P = 0.007) and 0.40 (P = 0.011), and local recurrence respectively, after adjustment for radiation therapy (RT) dose, whereas the RR of mortality adjusted for RT and study was 0.68 (P = 0.17). The 20-year risk of CHF after primary DOX treatment on NWTS-3 and NWTS-4 was 1.2%. CONCLUSIONS: The inclusion of data from nonrandomized patients yielded estimates of DOX treatment effects for Stage III/FH WT that were stronger, albeit more susceptible to bias, than reported previously. Despite a lower reported risk of CHF, conclusive evidence that frontline therapy with DOX definitively improves survival remains elusive. Copyright 2004 American Cancer Society.
Authors: Marry M van den Heuvel-Eibrink; Janna A Hol; Kathy Pritchard-Jones; Harm van Tinteren; Rhoikos Furtwängler; Arnauld C Verschuur; Gordan M Vujanic; Ivo Leuschner; Jesper Brok; Christian Rübe; Anne M Smets; Geert O Janssens; Jan Godzinski; Gema L Ramírez-Villar; Beatriz de Camargo; Heidi Segers; Paola Collini; Manfred Gessler; Christophe Bergeron; Filippo Spreafico; Norbert Graf Journal: Nat Rev Urol Date: 2017-10-31 Impact factor: 14.432
Authors: Peter F Ehrlich; James R Anderson; Michael L Ritchey; Jeffrey S Dome; Daniel M Green; Paul E Grundy; Elizabeth J Perlman; John A Kalapurakal; Norman E Breslow; Robert C Shamberger Journal: J Clin Oncol Date: 2013-02-04 Impact factor: 44.544
Authors: Jeffrey S Dome; Conrad V Fernandez; Elizabeth A Mullen; John A Kalapurakal; James I Geller; Vicki Huff; Eric J Gratias; David B Dix; Peter F Ehrlich; Geetika Khanna; Marcio H Malogolowkin; James R Anderson; Arlene Naranjo; Elizabeth J Perlman Journal: Pediatr Blood Cancer Date: 2012-12-19 Impact factor: 3.167
Authors: Norman E Breslow; J Bruce Beckwith; Gerald M Haase; John A Kalapurakal; Michael L Ritchey; Robert C Shamberger; Patrick R M Thomas; Giulio J D'Angio; Daniel M Green Journal: Int J Radiat Oncol Biol Phys Date: 2006-03-20 Impact factor: 7.038
Authors: Chiang-Ching Huang; Samantha Gadd; Norman Breslow; Colleen Cutcliffe; Simone T Sredni; Irene B Helenowski; Jeffrey S Dome; Paul E Grundy; Daniel M Green; Michael K Fritsch; Elizabeth J Perlman Journal: Clin Cancer Res Date: 2009-02-10 Impact factor: 12.531
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