Doxorubicin for favorable histology, Stage II-III Wilms tumor: results from the National Wilms Tumor Studies.
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.
Department of Biostatistics, University of Washington, Seattle 98195-7232, USA. norm@u.washington.edu
Norman E
NE
Breslow
San-San
SS
Ou
J Bruce
JB
Beckwith
Gerald M
GM
Haase
John A
JA
Kalapurakal
Michael L
ML
Ritchey
Robert C
RC
Shamberger
Patrick R M
PR
Thomas
Giulio J
GJ
D'Angio
Daniel M
DM
Green
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003609:Dactinomycin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D006333:Heart Failure / Q000209:etiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D009367:Neoplasm Staging; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D009396:Wilms Tumor / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy
D003609:Dactinomycin; D014750:Vincristine; D004317:Doxorubicin