NWTS-2

Background

Phase III RCT (National Wilms Tumor Study-2, NWTS-2). 513 children with Wilms tumor. Evaluated whether doxorubicin adds benefit to vincristine + dactinomycin, and examined role of RT in different stages. Second major NWTS trial following NWTS-1. Enrolled 1974–1978.

Interventions and follow up

Arm A: Vincristine + dactinomycin × 15 months (no doxorubicin)
Arm B: Vincristine + dactinomycin + doxorubicin × 15 monthsRT: Stage I–II: no RT (favorable histology); Stage III–IV: flank or whole abdomen RT 20 Gy
Primary endpoint: Relapse-free survival, OS
mFollow up: 5.0 year

Results

4-yr RFS (doxorubicin arm, stage III–IV): 77% vs no doxorubicin 56%, P<.01
4-yr OS: 83% (doxorubicin) vs 73% (no doxorubicin), P=.03
Stage I favorable histology (no RT): 4-yr RFS 92% — RT omission safe

Adverse events

Main adverse events: Doxorubicin: cardiotoxicity (acute CHF 2%), myelosuppression. RT: scoliosis (flank RT in young children), ovarian dysfunction. Combined modality toxicity modest in this era with lower doxorubicin doses.

Conclusions

Doxorubicin significantly improved outcomes for stage III–IV Wilms tumor. Stage I favorable histology could be treated without RT — confirming NWTS-1 findings. This established the three-drug backbone (vincristine/dactinomycin/doxorubicin = DD-4A equivalent) for higher-stage disease.

Key Limitations

Key Limitations: Treatment era (1974–1978); diagnostic imaging and surgical techniques substantially different from modern practice. Histologic classification predates blastemal predominance recognition. Pathologic review was not centralized to same degree as modern trials.

Clinical Context

NWTS-2 established the chemotherapy backbone for Wilms tumor still in use today. Three-drug therapy (vincristine/dactinomycin/doxorubicin) for stage III–IV and RT omission for stage I favorable histology are current standards traceable to this trial.

References

References: D'Angio GJ et al, Cancer 1981 (NWTS-2)