Current experience with mIBG therapy in combination with chemotherapy and radiosensitizers

Introduction: [¹³¹I]meta-iodobenzylguanidine ([¹³¹I]mIBG) has been used for decades to treat childhood neuroblastoma and adult neuroendocrine tumors, which express the norepinephrine transporter molecule. The scheduling has changed over time in attempts to improve its efficacy. The treatment intent has gone beyond simple palliation to the use of mIBG as part of a radical potentially curative approach in some patients. As chemotherapy is an established part of the treatment of high-risk neuroblastoma and mIBG works through a different mechanism, there is a rationale for combining these treatments. If there is no interaction, an additive effect may be seen. Some drugs interfere with repair of DNA damaged by radiation and act as radiation sensitizers so will be synergistic with mIBG therapy. Methods: A literature search was undertaken to identify published reports of the use of mIBG therapy in both neuroblastoma and adult neuroendocrine tumors in combination with chemotherapy or radiosensitizers. The resulting literature has been reviewed and interpreted. Results: There are convincing preclinical data to suggest that the combined use of mIBG and chemotherapy and radiosensitizers may be synergistic. Phase 1 and 2 series indicate that such combinations are practicable to deliver at both conventional doses and with high-dose schedules requiring hemopoietic support. However, there are as yet no randomized phase 3 trials proving the superiority of combined treatments over mIBG alone. Conclusions: Large-scale clinical trials are required to ascertain whether the synergy of combined mIBG and chemotherapy treatment schedules predicted by preclinical studies occurs in clinical practice