Tumor response and toxicity with multiple infusions of high dose 131I-MIBG for refractory neuroblastoma.
BACKGROUND
(131)I Metaiodobenzylguanidine ((131)I-MIBG) is an effective targeted radiotherapeutic for neuroblastoma with response rates greater than 30% in refractory disease. Toxicity is mainly limited to myelosuppression. The aim of this study was to determine the response rate and hematologic toxicity of multiple infusions of (131)I-MIBG.


METHODS
Patients received two to four infusions of (131)I-MIBG at activity levels of 3-19 mCi/kg per infusion. Criteria for subsequent infusions were neutrophil recovery without stem cell support and lack of disease progression after the first infusion.


RESULTS
Sixty-two infusions were administered to 28 patients, with 24 patients receiving two infusions, two patients receiving three infusions, and two patients receiving four infusions. All patients were heavily pre-treated, including 16 with prior myeloablative therapy. Eleven patients (39%) had overall disease response to multiple therapies, including eight patients with measurable responses to each of two or three infusions, and three with a partial response (PR) after the first infusion and stable disease after the second. The main toxicity was myelosuppression, with 78% and 82% of patients requiring platelet transfusion support after the first and second infusion, respectively, while only 50% had grade 4 neutropenia, usually transient. Thirteen patients did not recover platelet transfusion independence after their final MIBG infusion; stem cell support was given in ten patients.


CONCLUSIONS
Multiple therapies with (131)I-MIBG achieved increasing responses, but hematologic toxicity, especially to platelets, was dose limiting. More effective therapy might be given using consecutive doses in rapid succession with early stem cell support.
Howard
James P
JP
Department of Pediatrics, University of California San Francisco School of Medicine and UCSF Children's Hospital, San Francisco, California, USA.
Maris
John M
JM
Kersun
Leslie S
LS
Huberty
John P
JP
Cheng
Su-Chun
SC
Hawkins
Randall A
RA
Matthay
Katherine K
KK
D019797:3-Iodobenzylguanidine / Q000008:administration & dosage* / Q000633:toxicity*; D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000139:chemically induced; D001853:Bone Marrow / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000633:toxicity*; D008297:Male; D009447:Neuroblastoma / Q000532:radiotherapy*; D009503:Neutropenia / Q000139:chemically induced; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000633:toxicity*; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine