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Conference Paper: Safety and Systemic Availability of Intravenous and Oral Arsenic Trioxide (As2O3) in Children with Relapsed / Refractory Neuroblastoma

TitleSafety and Systemic Availability of Intravenous and Oral Arsenic Trioxide (As2O3) in Children with Relapsed / Refractory Neuroblastoma
Authors
Issue Date2004
Citation
The 11th Annual Meeting of Advances in Neuroblastoma Research Association, Genova, Italy, 16-19 June 2004 How to Cite?
AbstractObjective: We conducted a phase I study to evaluate the safety and bioavailability of intravenous (IV) and per oral (PO) As2O3 in children with neuroblastoma. Method: Eleven children with neuroblastoma were recruited (mean age 2.5 yrs [range 2.1 to 5 yrs, M:F=5:6]). All were previously treated with modified N6/N7 chemotherapy regimen, 3F8 immunotherapy, local irradiation plus auto-PBSCT (n=6), topotecan (n=2) & others (n=1). A maximum of 5 courses would be given and each consisted of 14 days of daily As2O3 alternated with 14 days of rest. In course one, 0.15mg/Kg As2O3 was given as 1 hour IV infusion and then shifted to PO route on Day 2, the rest of the course was by IV route. Blood samples for pharmacokinetic study were taken 0,1,2,4,6 & 8 hours on Days 1 & 2 and 0 hour on Day 3. Blood plasma and cellular fractions were freshly separated and arsenic concentrations were determined in duplicate by inductively coupled plasma-mass spectrometry. Results: A total of 33 courses of As2O3 were given (3 received 5 courses). The estimated 3 yrs progression free survival was 18% by Kaplan-Meier estimation (2/11 survived at 3yrs, median survival 11 months). In 5/11 tested, plasma and cell samples showed comparable area under the curve attributable to IV or PO dosing. However, the profile of concentrations (peak 400-600 nM) suggested that higher dosage is needed to achieve adequate anti-tumor effect based on in-vitro data for neuroblastoma (2000 nM). No significant side effects were found. Conclusions: Children could achieve similar plasma and cellular concentration of As2O3 by either IV or PO route. Using the current dosage, the peak and trough concentration of As2O3 were lower than anticipated concentrations required in-vitro.
Persistent Identifierhttp://hdl.handle.net/10722/102921

 

DC FieldValueLanguage
dc.contributor.authorChan, CFen_HK
dc.contributor.authorYuen, WHen_HK
dc.contributor.authorCheung, GTYen_HK
dc.contributor.authorWong, WIen_HK
dc.contributor.authorNg, MWen_HK
dc.contributor.authorKwong, YLen_HK
dc.contributor.authorLau, YLen_HK
dc.contributor.authorMan, RYKen_HK
dc.contributor.authorKumana, CRen_HK
dc.date.accessioned2010-09-25T20:50:16Z-
dc.date.available2010-09-25T20:50:16Z-
dc.date.issued2004en_HK
dc.identifier.citationThe 11th Annual Meeting of Advances in Neuroblastoma Research Association, Genova, Italy, 16-19 June 2004-
dc.identifier.urihttp://hdl.handle.net/10722/102921-
dc.description.abstractObjective: We conducted a phase I study to evaluate the safety and bioavailability of intravenous (IV) and per oral (PO) As2O3 in children with neuroblastoma. Method: Eleven children with neuroblastoma were recruited (mean age 2.5 yrs [range 2.1 to 5 yrs, M:F=5:6]). All were previously treated with modified N6/N7 chemotherapy regimen, 3F8 immunotherapy, local irradiation plus auto-PBSCT (n=6), topotecan (n=2) & others (n=1). A maximum of 5 courses would be given and each consisted of 14 days of daily As2O3 alternated with 14 days of rest. In course one, 0.15mg/Kg As2O3 was given as 1 hour IV infusion and then shifted to PO route on Day 2, the rest of the course was by IV route. Blood samples for pharmacokinetic study were taken 0,1,2,4,6 & 8 hours on Days 1 & 2 and 0 hour on Day 3. Blood plasma and cellular fractions were freshly separated and arsenic concentrations were determined in duplicate by inductively coupled plasma-mass spectrometry. Results: A total of 33 courses of As2O3 were given (3 received 5 courses). The estimated 3 yrs progression free survival was 18% by Kaplan-Meier estimation (2/11 survived at 3yrs, median survival 11 months). In 5/11 tested, plasma and cell samples showed comparable area under the curve attributable to IV or PO dosing. However, the profile of concentrations (peak 400-600 nM) suggested that higher dosage is needed to achieve adequate anti-tumor effect based on in-vitro data for neuroblastoma (2000 nM). No significant side effects were found. Conclusions: Children could achieve similar plasma and cellular concentration of As2O3 by either IV or PO route. Using the current dosage, the peak and trough concentration of As2O3 were lower than anticipated concentrations required in-vitro.-
dc.languageengen_HK
dc.relation.ispartofAnnual Meeting of Advances in Neuroblastoma Research Associationen_HK
dc.titleSafety and Systemic Availability of Intravenous and Oral Arsenic Trioxide (As2O3) in Children with Relapsed / Refractory Neuroblastomaen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailYuen, WH: whyuen@srpdfond.comen_HK
dc.identifier.emailNg, MW: dianeng@graduate.hku.hken_HK
dc.identifier.emailKwong, YL: ylkwong@hku.hken_HK
dc.identifier.emailLau, YL: siulamlau@sinagirl.comen_HK
dc.identifier.emailMan, RYK: rykman@hkucc.hku.hken_HK
dc.identifier.emailKumana, CR: hrmekcr@hku.hken_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.identifier.authorityMan, RYK=rp00236en_HK
dc.identifier.hkuros108038en_HK

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