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

Autor:	DuBois SG; Department of Pediatrics, UCSF School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA 94143, USA., Allen S; Department of Pediatrics, UCSF School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA 94143, USA., Bent M; Department of Pediatrics, UCSF School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA 94143, USA., Hilton JF; Department of Epidemiology and Biostatistics, UCSF School of Medicine, San Francisco, CA 94143, USA., Hollinger F; Department of Pediatrics, UCSF School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA 94143, USA., Hawkins R; Department of Radiology, UCSF School of Medicine, San Francisco, CA 94143, USA., Courtier J; Department of Radiology, UCSF School of Medicine, San Francisco, CA 94143, USA., Mosse YP; Department of Pediatrics, University of Pennsylvania School of Medicine and Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA., Matthay KK; Department of Pediatrics, UCSF School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA 94143, USA.
Jazyk:	angličtina
Zdroj:	British journal of cancer [Br J Cancer] 2015 Feb 17; Vol. 112 (4), pp. 644-9. Date of Electronic Publication: 2015 Jan 20.
DOI:	10.1038/bjc.2015.12
Abstrakt:	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. Methods: Patients 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. Results: Thirty-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. Conclusions: MIBG (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:	MEDLINE
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