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

Purpose

We report the results of the French multicentric phase II study MIITOP (NCT00960739), which evaluated tandem infusions of ¹³¹I-metaiodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory metastatic neuroblastoma (NBL).

Methods

Patients received ¹³¹I-mIBG on day 1, with intravenous topotecan daily on days 1–5. A second activity of ¹³¹I-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.

Results

Thirty 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).

Conclusion

MIITOP showed acceptable tolerability in this heavily pretreated population and encouraging survival rates in VHR-NBL when followed by busulfan-melphalan.