Premium
Dose‐response effect of eribulin in preclinical models of osteosarcoma by the pediatric preclinical testing consortium
Author(s) -
Gill Jonathan,
Zhang Wendong,
Zhang Zhongting,
Roth Michael,
Harrison Douglas J.,
Rowshan Sudie,
Erickson Stephen,
Gatto Gregory,
Kurmasheva Raushan,
Houghton Peter,
Teicher Beverly,
Smith Malcolm A.,
Kolb E. Anders,
Gorlick Richard
Publication year - 2020
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.28606
Subject(s) - eribulin , medicine , osteosarcoma , oncology , preclinical testing , blood cancer , pharmacology , cancer , cancer research , medical physics , metastatic breast cancer , breast cancer
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.