Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane®) by the Pediatric Preclinical Testing Program (PPTP)

Peter J. Houghton, Raushan T. Kurmasheva, E. Anders Kolb, Richard Gorlick, John M. Maris, Jianrong Wu, Zeen Tong, Michael A. Arnold, Moumita Chatterjee, Terence M. Williams, Malcolm A. Smith

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Background: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel, Abraxane®) is FDA approved for the treatment of several adult cancers. Antimitotic agents are essential components for curative therapy of pediatric solid tumors, although taxanes have shown limited activity. Because of the novel formulation, nab-paclitaxel was evaluated against a limited series of Pediatric Preclinical Testing Program (PPTP) solid tumors. Procedures: Nab-paclitaxel was tested against a limited subset of PPTP solid tumor xenograft models at a dose of 50mg/kg using a q4d×3 schedule intravenously. Results: Nab-paclitaxel was well tolerated in vivo, producing maximum weight loss of approximately 10% with recovery to baseline weight in the week following the third dose. All 20 xenograft models tested were considered evaluable for efficacy. Nab-paclitaxel induced statistically significant differences in event-free survival (EFS) distribution compared to control in 19 of 20 (95%) of the solid tumors. Objective responses were observed in 12 of 20 (60%) solid tumor xenografts. Complete responses (CR) or maintained CR were observed in 5 of 8 Ewing sarcoma models and 6 of 8 rhabdomyosarcomas. There were no objective regressions in either neuroblastoma (n=2) or osteosarcoma (n=2) xenograft panels. At the dose tested, systemic exposures of nab-paclitaxel in mice were somewhat greater than those tolerated in humans. Conclusions: The high level of activity observed against the rhabdomyosarcoma and Ewing sarcoma PPTP preclinical models makes nab-paclitaxel an interesting agent to consider for pediatric evaluation. Pediatr Blood Cancer 2015;62:1214-1221.

Original languageEnglish (US)
Pages (from-to)1214-1221
Number of pages8
JournalPediatric Blood and Cancer
Volume62
Issue number7
DOIs
StatePublished - Jul 1 2015

Keywords

  • Abraxane
  • Developmental therapeutics
  • Preclinical testing
  • nab-paclitaxel

ASJC Scopus subject areas

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

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    Houghton, P. J., Kurmasheva, R. T., Kolb, E. A., Gorlick, R., Maris, J. M., Wu, J., Tong, Z., Arnold, M. A., Chatterjee, M., Williams, T. M., & Smith, M. A. (2015). Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane®) by the Pediatric Preclinical Testing Program (PPTP). Pediatric Blood and Cancer, 62(7), 1214-1221. https://doi.org/10.1002/pbc.25474