Doxorubicin for favorable histology, stage II-III Wilms tumor results from the National Wilms Tumor Studies

Norman E. Breslow*, San San Ou, 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

*Corresponding author for this work

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1072-1080
Number of pages9
JournalCancer
Volume101
Issue number5
DOIs
StatePublished - Sep 1 2004

Keywords

  • Congestive heart failure
  • Historical controls
  • Recurrence
  • Retrieval
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Breslow, N. E., Ou, S. S., Beckwith, J. B., Haase, G. M., Kalapurakal, J. A., Ritchey, M. L., Shamberger, R. C., Thomas, P. R. M., D'Angio, G. J., & Green, D. M. (2004). Doxorubicin for favorable histology, stage II-III Wilms tumor results from the National Wilms Tumor Studies. Cancer, 101(5), 1072-1080. https://doi.org/10.1002/cncr.20433