학술논문

Phase I/II study of 131I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma
Document Type
article
Source
British Journal of Cancer. 112(4)
Subject
Biomedical and Clinical Sciences
Clinical Sciences
Stem Cell Research - Nonembryonic - Human
Neuroblastoma
Cancer
Clinical Research
Pediatric
Pediatric Cancer
Clinical Trials and Supportive Activities
Neurosciences
Stem Cell Research
Rare Diseases
6.1 Pharmaceuticals
Evaluation of treatments and therapeutic interventions
3-Iodobenzylguanidine
Adolescent
Adult
Antineoplastic Combined Chemotherapy Protocols
Camptothecin
Chemoradiotherapy
Child
Child
Preschool
Dose-Response Relationship
Drug
Drug Administration Schedule
Female
Humans
Iodine Radioisotopes
Irinotecan
Male
Maximum Tolerated Dose
Radiotherapy Dosage
Vincristine
Young Adult
I-131-MIBG
irinotecan
vincristine
neuroblastoma
UGT1A1
Oncology and Carcinogenesis
Public Health and Health Services
Oncology & Carcinogenesis
Oncology and carcinogenesis
Language
Abstract
Background(131)I-metaiodobenzylguanidine (MIBG) is an active radiopharmaceutical in neuroblastoma. A previous study demonstrated that MIBG could be combined with vincristine and prolonged irinotecan, although 25% of first courses had grade 3 diarrhoea. The current phase I/II study evaluated MIBG with vincristine and 5 days of higher-dose irinotecan.MethodsPatients 1-30 years old with advanced neuroblastoma were eligible. Patients received cefixime on days -1 to +6, irinotecan (50 mg m(-2) per dose IV) on days 0-4, vincristine (2 mg m(-2)) on day 0, MIBG (555 or 666 MBq kg(-1)) on day 1, and peripheral blood stem cells on day 13. UGT1A1 genotyping was performed in consenting patients.ResultsThirty-two patients (12 phase I ; 20 phase II) received 42 courses. No dose-limiting toxicities were seen during dose escalation and the recommended administered activity was 666 MBq kg(-1). Myelosuppression and diarrhoea were the most common toxicities, with grade 3 diarrhoea in 6% of first courses. Patients homozygous for UGT1A1*28 had more grade 4 thrombocytopenia (80% vs 37%; P=0.14). Responses (five complete and four partial) occurred in 9 out of 32 (28%) patients.ConclusionsMIBG (666 MBq kg(-1)) with vincristine and this irinotecan schedule is tolerable and active, with less severe diarrhoea compared with a regimen using more protracted irinotecan.