A nationwide phase II study of delayed local treatment for children with high‐risk neuroblastoma: The Japan Children's Cancer Group Neuroblastoma Committee Trial JN‐H‐11

Abstract Purpose Survival rates of patients with high‐risk neuroblastoma are unacceptable. A time‐intensified treatment strategy with delayed local treatment to control systemic diseases has been developed in Japan. We conducted a nationwide, prospective, single‐arm clinical trial with delayed local treatment. This study evaluated the safety and efficacy of delayed surgery to increase treatment intensity. Patients and methods Seventy‐five patients with high‐risk neuroblastoma were enrolled in this study between May 2011 and September 2015. Delayed local treatment consisted of five courses of induction chemotherapy (cisplatin, pirarubicin, vincristine, and cyclophosphamide) and myeloablative high‐dose chemotherapy (melphalan, etoposide, and carboplatin), followed by local tumor extirpation with surgery and irradiation. The primary endpoint was progression‐free survival (PFS). The secondary endpoints were overall survival (OS), response rate, adverse events, and surgical complications. Results Seventy‐five patients were enrolled, and 64 were evaluable (stage 3, n = 8; stage 4, n = 56). The estimated 3‐year PFS and OS rates (95% confidence interval CI) were 44.4% 31.8%–56.3% and 80.7% 68.5%–88.5%, resspectively. The response rate of INRC after completion of the treatment protocol was 66% (42/64; 95% CI: 53%–77%; 23 CR complete response, 10 VGPR very good partial response, and nine PR partial response). None of the patients died during the protocol treatment or within 30 days of completion. Grade 4 adverse effects, excluding hematological adverse effects, occurred in 48% of patients 31/64; 95% CI: 36%–61%. Major Surgical complications were observed in 25% of patients 13/51; 95% CI: 14%–40%. Conclusion This study indicates that delayed local treatment is feasible and shows promising efficacy, suggesting that this treatment should be considered further in a comparative study of high‐risk neuroblastoma.