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Evaluation of arsenic trioxide by the pediatric preclinical testing program with a focus on Ewing sarcoma.

ABSTRACT: Arsenic trioxide was tested against the PPTP in vitro panel (1.0 nM to 10 µM) and against the PPTP Ewing sarcoma in vivo panel administered intraperitoneally at a dose of 2.5 mg/kg daily × 5 per week for a planned treatment duration of 3 weeks. Arsenic trioxide showed a median relative IC(50) value of 0.9 µM, with Ewing sarcoma cell lines having IC(50) values similar to those of the remaining PPTP cell lines. Arsenic trioxide did not induce significant differences in EFS distribution compared to control in any of the Ewing sarcoma xenografts studied, and no objective responses were observed.

SUBMITTER: Smith MA

PROVIDER: S-EPMC3612422 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Evaluation of arsenic trioxide by the pediatric preclinical testing program with a focus on Ewing sarcoma.

Smith Malcolm A MA Kang Min H MH Reynolds C Patrick CP Kurmasheva Raushan T RT Alexander Denise D Billups Catherine A CA Toretsky Jeffrey A JA Houghton Peter J PJ

Pediatric blood & cancer 20120207 4

Arsenic trioxide was tested against the PPTP in vitro panel (1.0 nM to 10 µM) and against the PPTP Ewing sarcoma in vivo panel administered intraperitoneally at a dose of 2.5 mg/kg daily × 5 per week for a planned treatment duration of 3 weeks. Arsenic trioxide showed a median relative IC(50) value of 0.9 µM, with Ewing sarcoma cell lines having IC(50) values similar to those of the remaining PPTP cell lines. Arsenic trioxide did not induce significant differences in EFS distribution compared to ...[more]

PMID: 22315235

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Evaluation of VTP-50469, a menin-MLL1 inhibitor, against Ewing sarcoma xenograft models by the pediatric preclinical testing consortium.

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Initial testing of lenalidomide by the pediatric preclinical testing program.

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Initial testing of topotecan by the pediatric preclinical testing program.

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Initial testing (stage 1) of lapatinib by the pediatric preclinical testing program.

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Initial testing (stage 1) of temozolomide by the pediatric preclinical testing program.

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Initial testing of the MDM2 inhibitor RG7112 by the Pediatric Preclinical Testing Program.

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Initial testing (stage 1) of vorinostat (SAHA) by the pediatric preclinical testing program.

Project description:Vorinostat, a histone deacetylase inhibitor, was evaluated against the in vitro and in vivo childhood solid tumor and leukemia models in the Pediatric Preclinical Testing Program (PPTP). In vitro testing was performed by the DIMSCAN cytotoxicity assay. In vivo, vorinostat was administered intraperitoneally to mice bearing xenografts. Vorinostat demonstrated 2-log cell growth inhibitory activity in vitro, but generally at concentrations not sustainable in the clinic. No objective responses were observed for any of the solid tumor or acute lymphoblastic leukemia xenografts. Preclinical studies with appropriate drug combinations may provide direction for further clinical evaluations of vorinostat against selected pediatric cancers.

| S-EPMC2752378 | biostudies-literature

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