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

Research output: Contribution to journalArticlepeer-review

1 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 languageEnglish (US)
Article numbere28606
JournalPediatric Blood and Cancer
Volume67
Issue number10
DOIs
StatePublished - Oct 1 2020

Keywords

  • PDX
  • eribulin
  • osteosarcoma

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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