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Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP).
- Source :
-
Pediatric blood & cancer [Pediatr Blood Cancer] 2015 Jul; Vol. 62 (7), pp. 1214-21. Date of Electronic Publication: 2015 Mar 23. - Publication Year :
- 2015
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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.<br />Procedures: Nab-paclitaxel was tested against a limited subset of PPTP solid tumor xenograft models at a dose of 50 mg/kg using a q4d × 3 schedule intravenously.<br />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.<br />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.<br /> (© 2015 Wiley Periodicals, Inc.)
- Subjects :
- Adult
Albumins pharmacology
Animals
Caveolin 1 genetics
Caveolin 1 metabolism
Child
Female
Humans
Immunoenzyme Techniques
Mice
Mice, SCID
Nanoparticles chemistry
Osteonectin genetics
Osteonectin metabolism
Paclitaxel pharmacology
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Sarcoma, Experimental genetics
Sarcoma, Experimental metabolism
Tissue Distribution
Tumor Cells, Cultured
Albumins pharmacokinetics
Nanoparticles administration & dosage
Paclitaxel pharmacokinetics
Sarcoma, Experimental drug therapy
Tubulin metabolism
Xenograft Model Antitumor Assays
Subjects
Details
- Language :
- English
- ISSN :
- 1545-5017
- Volume :
- 62
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Pediatric blood & cancer
- Publication Type :
- Academic Journal
- Accession number :
- 25809532
- Full Text :
- https://doi.org/10.1002/pbc.25474