Phase I/II study of 131I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma

Autor: Steven G. DuBois, Yael P. Mosse, F Hollinger, S Allen, Katherine K. Matthay, Joan F. Hilton, Randy Hawkins, M Bent, Jesse Courtier
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Oncology
Male
Cancer Research
Pharmacology
I-131-MIBG
3-Iodobenzylguanidine
Iodine Radioisotopes
Neuroblastoma
Stem Cell Research - Nonembryonic - Human
Antineoplastic Combined Chemotherapy Protocols
Child
Cancer
Pediatric
131I-MIBG
Radiotherapy Dosage
Chemoradiotherapy
3. Good health
6.1 Pharmaceuticals
Child
Preschool
Public Health and Health Services
Female
Drug
medicine.drug
Adult
Vincristine
medicine.medical_specialty
Adolescent
Maximum Tolerated Dose
Pediatric Cancer
Clinical Trials and Supportive Activities
Oncology and Carcinogenesis
Irinotecan
vincristine
Drug Administration Schedule
Dose-Response Relationship
neuroblastoma
Young Adult
Rare Diseases
Clinical Research
Internal medicine
medicine
Humans
Oncology & Carcinogenesis
Preschool
Dose-Response Relationship
Drug
business.industry
Neurosciences
Evaluation of treatments and therapeutic interventions
medicine.disease
Stem Cell Research
Phase i ii
Maximum tolerated dose
Clinical Study
Camptothecin
UGT1A1
business
Zdroj: British Journal of Cancer
British journal of cancer, vol 112, iss 4
ISSN: 1532-1827
0007-0920
Popis: 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.
Databáze: OpenAIRE
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