Phase I study of vincristine, irinotecan, and ¹³¹I-metaiodobenzylguanidine for patients with relapsed or refractory neuroblastoma: a new approaches to neuroblastoma therapy trial.

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TitlePhase I study of vincristine, irinotecan, and ¹³¹I-metaiodobenzylguanidine for patients with relapsed or refractory neuroblastoma: a new approaches to neuroblastoma therapy trial.
Publication TypeJournal Article
Year of Publication2012
AuthorsDuBois, SG, Chesler, L, Groshen, S, Hawkins, R, Goodarzian, F, Shimada, H, Yanik, G, Tagen, M, Stewart, C, Mosse, YP, Maris, JM, Tsao-Wei, D, Marachelian, A, Villablanca, JG, Matthay, KK
JournalClin Cancer Res
Volume18
Issue9
Pagination2679-86
Date Published2012 May 1
ISSN1078-0432
Keywords3-Iodobenzylguanidine, Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Iodine Radioisotopes, Male, Maximum Tolerated Dose, Neuroblastoma, Prognosis, Tissue Distribution, Vincristine, Young Adult
Abstract

PURPOSE: (131)I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical with activity in patients with relapsed or refractory neuroblastoma. Irinotecan is a known radiosensitizer with activity in neuroblastoma. This phase I study aimed to determine the recommended phase 2 dose of MIBG together with fixed doses of vincristine and irinotecan. EXPERIMENTAL DESIGN: Patients 1 to 30 years old with relapsed or refractory neuroblastoma and MIBG-avid tumors were eligible. All patients had autologous hematopoietic stem cells (PBSC) available and met standard phase I organ function requirements. Irinotecan (20 mg/m(2)/dose IV) was given on days 0 to 4 and 7 to 11, with vincristine (1.5 mg/m(2) IV) on days 0 and 7. MIBG was given on day 1 following a 3 + 3 phase I dose escalation design starting at 8 mCi/kg MIBG. PBSCs were administered at dose level 8 mCi/kg for prolonged myelosuppression and for all patients at 12 mCi/kg or more. RESULTS: Twenty-four patients evaluable for dose escalation (median age, 6.7 years; range, 1.9-26.8 years) received 1 (n = 17), 2 (n = 5), or 3 (n = 2) cycles of therapy. Myelosuppression and diarrhea were the most common toxicities. Two of 6 patients at the 18 mCi/kg dose level had dose-limiting toxicity (DLT), including one with protocol-defined DLT with prolonged mild aspartate aminotransferase elevation. Eighteen mCi/kg was the recommended phase 2 dose. Six additional patients were treated at 18 mCi/kg, with one additional DLT. Responses (2 complete and 4 partial responses) occurred in 6 of 24 (25%) evaluable patients. CONCLUSIONS: MIBG is tolerable and active at 18 mCi/kg with standard doses of vincristine and irinotecan.

DOI10.1158/1078-0432.CCR-11-3201
Alternate JournalClin. Cancer Res.
PubMed ID22421195