The purpose of this study was to evaluate the effect of the sequential addition of doxorubicin and cyclophosphamide to the combination of vincristine and actinomycin D o n the relapse-free survival of children with stage IV/favorable histology Wilms tumor. We reviewed the clinical courses of all randomized patients from National Wilms Tumor Study (NWTS)-2 and 3 with stage IV/ favorable histology (FH) Wilms tumor. We determined the four-year relapse-free survival percentage for patients treated on NWS-2 with the combination of vincristine (VCR) and actinomycin D (AMD) with (regimen D) or without (regimen C) doxorubicin (DOX), and for patients treated on NWS-3 with the cornbination of VCR + AMD +DOX with (regimen J) or without (regimen DD-RT) cyclophosphamide (CTX). All children received whole lung radiation therapy.
The four-year relapse-free survival percentage for children with stage IV/FH Wilms tumor treated with regimen C was 53.3%, compared to 57.7% for those treated with regimen D (P = 0.63). The four-year relapse-free survival percentage for children with stage IV/FH Wilms tumor treated with regimen DD-RTwas 79.0%, compared to 80.9% for those treated on regimen J ( P = 0.79). the four-year relapsefree survival for children with lung metastases only treated with regimen D on NWTS-2 was significantly lower than that of children treated with the related regimen DD-RT on We conclude that the addition of doxorubicin to the combination of vincristine and actinomycin D and pulmonary irradiation did not clearly improve the four-year relapse-free survival percentage of children with stage IV/FH Wilms tumor, although the benefit may have been masked by the greater frequency of death due to toxicity in NWTS-2. There was no evidence that the addition of CfX to the threedrug treatment regimen improved the fouryear relapse-free survival percentage of children with stage IV/FH Wilms tumor. The data with only two drugs derived from NWTS-2 suggest that there is a population of children with stage IV/FH Wilms tumor who can be successfully treated without an anthracycline. The goal of future research will be to identify this subgroup at the time of initial diagnosis.
NWTS-3 (P = 0.03).