title: Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer.
abstract: OBJECTIVE
  ABI-007, the first biologically interactive albumin-bound paclitaxel in a nanameter particle, free of solvents, was compared with polyethylated castor oil-based standard paclitaxel in patients with metastatic breast cancer (MBC). This phase III study was performed to confirm preclinical studies demonstrating superior efficacy and reduced toxicity of ABI-007 compared with standard paclitaxel.
  
  
  METHODS
  Patients were randomly assigned to 3-week cycles of either ABI-007 260 mg/m(2) intravenously without premedication (n = 229) or standard paclitaxel 175 mg/m(2) intravenously with premedication (n = 225).
  
  
  RESULTS
  ABI-007 demonstrated significantly higher response rates compared with standard paclitaxel (33% v 19%, respectively; P = .001) and significantly longer time to tumor progression (23.0 v 16.9 weeks, respectively; hazard ratio = 0.75; P = .006). The incidence of grade 4 neutropenia was significantly lower for ABI-007 compared with standard paclitaxel (9% v 22%, respectively; P < .001) despite a 49% higher paclitaxel dose. Febrile neutropenia was uncommon (< 2%), and the incidence did not differ between the two study arms. Grade 3 sensory neuropathy was more common in the ABI-007 arm than in the standard paclitaxel arm (10% v 2%, respectively; P < .001) but was easily managed and improved rapidly (median, 22 days). No hypersensitivity reactions occurred with ABI-007 despite the absence of premedication and shorter administration time.
  
  
  CONCLUSIONS
  ABI-007 demonstrated greater efficacy and a favorable safety profile compared with standard paclitaxel in this patient population. The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC.
authors.affiliation: Northwestern University, Breast Oncology, Division of Hematology/Oncology, Department of Medicine, Chicago, IL 60611, USA. w-gradishar@northwestern.edu
authors.forename: William J
authors.initials: WJ
authors.lastname: Gradishar
authors.forename: Sergei
authors.initials: S
authors.lastname: Tjulandin
authors.forename: Neville
authors.initials: N
authors.lastname: Davidson
authors.forename: Heather
authors.initials: H
authors.lastname: Shaw
authors.forename: Neil
authors.initials: N
authors.lastname: Desai
authors.forename: Paul
authors.initials: P
authors.lastname: Bhar
authors.forename: Michael
authors.initials: M
authors.lastname: Hawkins
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
mesh_terms: D000328:Adult; D000368:Aged; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000009:adverse effects / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002368:Castor Oil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D049329:Nanostructures; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; C023040:polyethoxylated castor oil; D002368:Castor Oil; D017239:Paclitaxel