Dose-response effect of eribulin in preclinical models of osteosarcoma by the pediatric preclinical testing consortium

Jonathan Gill; Wendong Zhang; Zhongting Zhang; Michael Roth; Douglas J. Harrison; Sudie Rowshan; Stephen Erickson; Gregory Gatto; Raushan Kurmasheva; Peter Houghton; Beverly Teicher; Malcolm A. Smith; E. Anders Kolb; Richard Gorlick

doi:10.1002/pbc.28606

Dose-response effect of eribulin in preclinical models of osteosarcoma by the pediatric preclinical testing consortium

Jonathan Gill, Wendong Zhang, Zhongting Zhang, Michael Roth, Douglas J. Harrison, Sudie Rowshan, Stephen Erickson, Gregory Gatto, Raushan Kurmasheva, Peter Houghton, Beverly Teicher, Malcolm A. Smith, E. Anders Kolb, Richard Gorlick

Pediatrics

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

The pediatric preclinical testing program previously demonstrated activity of eribulin in osteosarcoma patient-derived xenograft (PDX) models. The phase 2 trial in patients with relapsed osteosarcoma failed to meet response endpoints. Eribulin was evaluated in the original and an expanded set of PDX models and tested at multiple dose levels and schedules to evaluate dose-response. Maximal response was observed at the highest dose, consistent with prior results. The alternative schedule generated similar responses. We demonstrate steep dose-response for eribulin in osteosarcoma PDX models, implying that any deviation from achievement of effective concentrations may have a significant impact on activity.

Original language	English (US)
Article number	e28606
Journal	Pediatric Blood and Cancer
Volume	67
Issue number	10
DOIs	https://doi.org/10.1002/pbc.28606
State	Published - Oct 1 2020

Keywords

PDX
eribulin
osteosarcoma

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

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10.1002/pbc.28606

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Gill, J., Zhang, W., Zhang, Z., Roth, M., Harrison, D. J., Rowshan, S., Erickson, S., Gatto, G., Kurmasheva, R., Houghton, P., Teicher, B., Smith, M. A., Kolb, E. A., & Gorlick, R. (2020). Dose-response effect of eribulin in preclinical models of osteosarcoma by the pediatric preclinical testing consortium. Pediatric Blood and Cancer, 67(10), Article e28606. https://doi.org/10.1002/pbc.28606

Gill, J, Zhang, W, Zhang, Z , Roth, M , Harrison, DJ, Rowshan, S, Erickson, S, Gatto, G, Kurmasheva, R, Houghton, P, Teicher, B, Smith, MA, Kolb, EA & Gorlick, R 2020, 'Dose-response effect of eribulin in preclinical models of osteosarcoma by the pediatric preclinical testing consortium', Pediatric Blood and Cancer, vol. 67, no. 10, e28606. https://doi.org/10.1002/pbc.28606

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AU - Zhang, Wendong

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AU - Roth, Michael

AU - Harrison, Douglas J.

AU - Rowshan, Sudie

AU - Erickson, Stephen

AU - Gatto, Gregory

AU - Kurmasheva, Raushan

AU - Houghton, Peter

AU - Teicher, Beverly

AU - Smith, Malcolm A.

AU - Kolb, E. Anders

AU - Gorlick, Richard

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AB - The pediatric preclinical testing program previously demonstrated activity of eribulin in osteosarcoma patient-derived xenograft (PDX) models. The phase 2 trial in patients with relapsed osteosarcoma failed to meet response endpoints. Eribulin was evaluated in the original and an expanded set of PDX models and tested at multiple dose levels and schedules to evaluate dose-response. Maximal response was observed at the highest dose, consistent with prior results. The alternative schedule generated similar responses. We demonstrate steep dose-response for eribulin in osteosarcoma PDX models, implying that any deviation from achievement of effective concentrations may have a significant impact on activity.

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Dose-response effect of eribulin in preclinical models of osteosarcoma by the pediatric preclinical testing consortium

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Keywords

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