Phase II study of 131I-metaiodobenzylguanidine with 5 days of topotecan for refractory or relapsed neuroblastoma: Results of the French study MIITOP

PurposeWe report the results of the French multicentric phase II study MIITOP (NCT00960739), which evaluated tandem infusions of I-131-metaiodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory metastatic neuroblastoma (NBL). MethodsPatients received I-131-mIBG on day 1, with intravenous topotecan daily on days 1-5. A second activity of I-131-mIBG was given on day 21 to deliver a whole-body radiation dose of 4 Gy, combined with a second course of topotecan on days 21-25. Peripheral blood stem cells were infused on day 31. ResultsThirty patients were enrolled from November 2008 to June 2015. Median age at diagnosis was 5.5 years (2-20). Twenty-one had very high-risk NBL (VHR-NBL), that is, stage 4 NBL at diagnosis or at relapse, with insufficient response (i.e., less than a partial response of metastases and more than three mIBG spots) after induction chemotherapy; nine had progressive metastatic relapse. Median Curie score at inclusion was 6 (1-26). Median number of prior lines of treatment was 3 (1-7). Objective response rate was 13% (95% confidence interval [CI]: 4-31) for the whole population, 19% for VHR-NBL, and 0% for progressive relapses. Immediate tolerance was good, with nonhematologic toxicity limited to grade-2 nausea/vomiting in eight patients. Two-year event-free survival was 17% (95% CI: 6-32). Among the 16 patients with VHR-NBL who had not received prior myeloablative busulfan-melphalan consolidation, 13 had at least stable disease after MIITOP; 11 subsequently received busulfan-melphalan; four of them were alive (median follow-up: 7 years). ConclusionMIITOP showed acceptable tolerability in this heavily pretreated population and encouraging survival rates in VHR-NBL when followed by busulfan-melphalan.