PHASE-I DOSE-ESCALATION OF I-131 METAIODOBENZYLGUANIDINE WITH AUTOLOGOUS BONE-MARROW SUPPORT IN REFRACTORY NEUROBLASTOMA

Purpose: The analogue (131)-metaiodobenxylguanidine (MIBG), which is s pecifically targeted to neuroblastoma cells, may provide more effectiv e and less toxic treatment for neuroblastoma than conventional externa l-beam radiotherapy. We report a dose escalation study of I-131-MIBG t o define dose-limiting toxicity without and with autologous bone marro w support. Patients and Methods: Thirty patients with relapsed neurobl astoma were treated in groups of six with escalating doses of 3 to 18 mCi/kg of I-131-MIBG. After rapid escalation in the first three patien ts treated at 3 to 6 mCi/kg, treatment was escalated in 3-mCi/kg incre ments from 9 to 18 mCi/kg. Autologous tumor-free bone marrow was cryop reserved in all patients receiving 12 mCi/kg and more. Toxicity and re sponse were assessed. Results: Eighty percent of patients who received 12 mCi/kg or more experienced grade 4 thrombocytopenia and/or neutrop enia. Dose-limiting hematologic toxicity wets reached at 15 mCi/kg, at which level two of five assessable patients required bone marrow rein fusion for absolute neutrophil count (ANC) of less than 280/mu L for m ore than 2 weeks, and four of nine at the 18-mCi/kg level. Prolonged t hrombocytopenia was common, with failure to become Platelet-transfusio n independent in nine patients. One patient with extensive prior treat ment developed secondary leukemia and three became hypothyroid, Respon ses were seen in 37% of patients, with one complete response (CR), 10 partial response (PR), three mixed response, 10 stable disease, and si x progressive disease. The minimum dose of I-131-MIBG for 10 of the 11 responders war 12 mCi/kg. Conclusion: Treatment with I-131-MIBG has m ainly hematologic toxicity, which can be abrogated with bone marrow re scue. The high response rate in refractory disease suggests that this agent may be useful in combination with myeloablative chemotherapy and autologous stem-cell rescue to improve outcome in advanced neuroblast oma. (C) 1998 by American Society of Clinical Oncology.