Dosimetry-based high-activity therapy with ${}^{131}$I-metaiodobenzylguanidine (${}^{131}$I-mIBG) and topotecan for the treatment of high-risk refractory neuroblastoma

Patients with high-risk neuroblastoma have an increased risk of recurrence and relapse of disease and a very poor prognosis. ${}^{131}$I-metaiodobenzylguanidine (${}^{131}$I-mIBG) in combination with topotecan as a radiosensitizer can be an effective and relatively well-tolerated agent for the treatment of refractory neuroblastoma. The aim of this retrospective study was to evaluate response and outcome of combined therapy with ${}^{131}$I-mIBG and topotecan. Ten patients, between 3 and 20 years of age, were included. Nine patients had been refractory to several lines of chemotherapy and radiotherapy. One patient with a very high-risk neuroblastoma had received only induction therapy. Response was graded according to the International Neuroblastoma Staging System. Regarding treatment response, two patients achieved complete remission, one with relapse at 16 months, five achieved a partial remission, four showed progression at between 1 and 18 months; two showed stable disease with progression at between 1 and 5 months, and one showed progressive disease. Eight of the ten patients died with overall survival between 4 and 63 months, and two patients were still alive without disease at the time of this report: 52 and 32 months (patient had received only induction therapy). Acute and subacute adverse effects were mainly haematological, and one patient developed a differentiated thyroid cancer. In patients with high-risk refractory neuroblastoma, administration of high activities of ${}^{131}$I-mIBG in combination with topotecan was found to be an effective therapy, increasing overall survival and progression-free survival. Further studies including a larger number of patients and using ${}^{131}$I-mIBG for first-line up-front therapy are warranted.