title: Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP).
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.
  
  
  METHODS
  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.
  
  
  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.
authors: Nationwide Children's Hospital, Columbus, Ohio.
authors: Peter J
authors: PJ
authors: Houghton
authors: Nationwide Children's Hospital, Columbus, Ohio.
authors: Raushan T
authors: RT
authors: Kurmasheva
authors: A.I. duPont Hospital for Children, Wilmington, Delaware.
authors: E Anders
authors: EA
authors: Kolb
authors: The Children's Hospital at Montefiore, Bronx, New York.
authors: Richard
authors: R
authors: Gorlick
authors: Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.|Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania.
authors: John M
authors: JM
authors: Maris
authors: St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Jianrong
authors: J
authors: Wu
authors: Celgene Corporation, Los Angeles, California.
authors: Zeen
authors: Z
authors: Tong
authors: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio.|Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio.
authors: Michael A
authors: MA
authors: Arnold
authors: James Cancer Hospital, Columbus, Ohio.
authors: Moumita
authors: M
authors: Chatterjee
authors: James Cancer Hospital, Columbus, Ohio.
authors: Terence M
authors: TM
authors: Williams
authors: Cancer Therapy Evaluation Program, NCI, Bethesda, Maryland.
authors: Malcolm A
authors: MA
authors: Smith
mesh_terms: D000328:Adult; D000418:Albumins / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014404:Tubulin / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D051242:Caveolin 1; D015676:Osteonectin; D012333:RNA, Messenger; C578250:SPARC protein, mouse; D014404:Tubulin; D017239:Paclitaxel
keywords: Abraxane; developmental therapeutics; nab-paclitaxel; preclinical testing