Introduction
131I‐meta‐iodobenzylguanidine (131I‐MIBG) is effective in relapsed neuroblastoma. The Children's Oncology Group (COG) conducted a pilot study (NCT01175356) to assess tolerability and feasibility of induction chemotherapy followed by 131I−MIBG therapy and myeloablative busulfan/melphalan (Bu/Mel) in patients with newly diagnosed high‐risk neuroblastoma.
Methods
Patients with MIBG‐avid high‐risk neuroblastoma were eligible. After the first two patients to receive protocol therapy developed severe sinusoidal obstruction syndrome (SOS), the trial was re‐designed to include an 131I‐MIBG dose escalation (12, 15, and 18 mCi/kg), with a required 10‐week gap before Bu/Mel administration. Patients who completed induction chemotherapy were evaluable for assessment of 131I‐MIBG feasibility; those who completed 131I‐MIBG therapy were evaluable for assessment of 131I‐MIBG + Bu/Mel feasibility.
Results
Fifty‐nine of 68 patients (86.8%) who completed induction chemotherapy received 131I‐MIBG. Thirty‐seven of 45 patients (82.2%) evaluable for 131I‐MIBG + Bu/Mel received this combination. Among those who received 131I‐MIBG after revision of the study design, one patient per dose level developed severe SOS. Rates of moderate to severe SOS at 12, 15, and 18 mCi/kg were 33.3%, 23.5%, and 25.0%, respectively. There was one toxic death. The 131I‐MIBG and 131I‐MIBG+Bu/Mel feasibility rates at the 15 mCi/kg dose level designated for further study were 96.7% (95% CI: 83.3%‐99.4%) and 81.0% (95% CI: 60.0%‐92.3%).
Conclusion
This pilot trial demonstrated feasibility and tolerability of administering 131I‐MIBG followed by myeloablative therapy with Bu/Mel to newly diagnosed children with high‐risk neuroblastoma in a cooperative group setting, laying the groundwork for a cooperative randomized trial (NCT03126916) testing the addition of 131I‐MIBG during induction therapy.