Timing and chemotherapy association for 131-I-MIBG treatment in high-risk neuroblastoma

Prognosis of high-risk neuroblastoma is dismal, despite intensive induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance. Patients who do not achieve a complete metastatic response, with clearance of bone marrow and skeletal NB infiltration, after induction have a significantly lower survival rate. Thus, it's necessary to further intensify treatment during this phase. 131-I-metaiodobenzylguanidine (131-I-MIBG) is a radioactive compound highly effective against neuroblastoma, with 32% response rate in relapsed/ resistant cases, and only hematological toxicity. 131-I-MIBG was utilized at different doses in single or multiple administrations, before autologous transplant or combined with high-dose chemotherapy. Subsequently, it was added to consolidation in patients with advanced NB after induction, but an independent contribution against neuroblastoma and for myelotoxicity is difficult to determine. Despite results of a 2008 paper demonstrated efficacy and mild hematological toxicity of 131-I-MIBG at diagnosis, no center had included it with intensive chemotherapy in first-line treatment protocols. In our institution, at diagnosis, 131-I-MIBG was included in a 5-chemotherapy drug combination and administered on day-10, at doses up to 18.3 mCi/kg. Almost 87% of objective responses were observed 50 days from start with acceptable hematological toxicity. In this paper, we review the literature data regarding 131-I-MIBG treatment for neuroblastoma, and report on doses and combinations used, tumor responses and toxicity. 131-I-MIBG is very effective against neuroblastoma, in particular if given to patients at diagnosis and in combination with chemotherapy, and it should be included in all induction regimens to improve early responses rates and consequently long-term survival.