Disease control intervals in high-risk neuroblastoma

BACKGROUND. Current salvage therapy for recurrent high-risk neuroblastoma is rarely curative. Assessment of the effectiveness of new, primarily cytostatic agents requires the redefinition of study endpoints to reflect disease stabilization rather than tumor response or regression. The intervals of disease control in the patients in the current study with recurrent neuroblastoma were characterized to provide comparison criteria for exploratory studies of new agents. METHODS. Disease control intervals, disease-free survival, postrecurrence survival, and median time to treatment failure were estimated in 90 patients with highrisk neuroblastoma treated between January 1991 and June 2002 on 3 St. Jude neuroblastoma protocols. RESULTS. The estimated median time to disease recurrence was 18.3 months (95% confidence interval [95% CI], 15.9-22.4 months) for the first recurrence, 8.7 months (95% CI, 5.0-12.2 months) for the second recurrence, and 3.8 months (95% CL 2.5-5.4 months) for the third recurrence. The 5-year estimate of survival after the first disease recurrence was 11% +/- 4%. Patients with longer initial disease control had a postrecurrence survival advantage:the 5-year estimated postrecurrence survival was 15.3% +/- 6.3% for patients with initial disease control >= 16 months and 8.1% +/- 5.5% for others (P = .006). The median disease control interval was approximately halved after each disease recurrence. CONCLUSIONS. The previous disease control interval should be considered in stratification schemes for future phase 2 testing of new agents for the treatment of neuroblastoma. For the optimal evaluation of new treatment strategies that incorporate cytostatic agents, study design and selection of endpoints must take into account the current patterns of recurrence or progression of neuroblastoma.