title: A randomized controlled phase II trial of a novel composition of paclitaxel embedded into neutral and cationic lipids targeting tumor endothelial cells in advanced triple-negative breast cancer (TNBC).
abstract: BACKGROUND
  EndoTAG-1, composed of paclitaxel embedded in liposomal membranes targeting tumor endothelial cells, was evaluated for safety and efficacy in advanced triple-negative breast cancer (TNBC).
  
  
  METHODS
  One hundred and forty patients were treated with weekly EndoTAG-1 (22 mg/m(2)) plus paclitaxel (70 mg/m(2)), twice weekly EndoTAG-1 (2× 44 mg/m(2)), or weekly paclitaxel (90 mg/m(2)) for greater than or equal to four cycles (3-week treatment + 1-week rest) or until progression/toxicity. Primary end point was progression-free survival (PFS) rate evaluated centrally after four cycles of therapy (week 16). The study was not powered for intergroup comparisons.
  
  
  RESULTS
  The PFS rate at week 16 was 59.1% [one-sided 95% CI: 45.6, ∞] on combination treatment, 34.2% [21.6, ∞] on EndoTAG-1, and 48.0% [30.5, ∞] on paclitaxel. Median PFS reached 4.2, 3.4, and 3.7 months, respectively. After complete treatment (week 41 analysis), median overall survival (OS) was 13.0, 11.9, and 13.1 months for the modified Intention-to-Treat (ITT) population and 15.1, 12.5, and 8.9 months for the per-protocol population, respectively. The clinical benefit rate was 53%, 31%, and 36% for the treatment groups. Safety analysis revealed known toxicities of the drugs with slight increases of grade 3/4 neutropenia on combination therapy.
  
  
  CONCLUSIONS
  Treatment of advanced TNBC with a combination of EndoTAG-1 and standard paclitaxel [Taxol® (Bristol-Myers Squibb GmbH), or equivalent generic formulation] was well tolerated and showed antitumor efficacy. The positive trend needs to be confirmed in a randomized phase III trial.
  
  
  BACKGROUND
  European Clinical Trials Database: EudraCT number 2006-002221-23. ClinicalTrials.gov identifier: NCT00448305.
authors.affiliation: Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium. Electronic address: ahmad.awada@bordet.be.
authors.forename: A
authors.initials: A
authors.lastname: Awada
authors.affiliation: Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine.
authors.forename: I N
authors.initials: IN
authors.lastname: Bondarenko
authors.affiliation: Oscar Lambret Center of Fight Against Cancer, Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Bonneterre
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Nowara
authors.affiliation: Antoine Lacassagne Center of Fight Against Cancer, Nice, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Ferrero
authors.affiliation: Kaushalya Medical Foundation, Thane, India.
authors.forename: A V
authors.initials: AV
authors.lastname: Bakshi
authors.affiliation: Medigene AG, Martinsried, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Wilke
authors.affiliation: Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Piccart
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D006801:Humans; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D008055:Lipids; D017239:Paclitaxel
keywords: EndoTAG-1; activated tumor endothelial cells; advanced disease; cationic liposomes of paclitaxel; lipid-embedded paclitaxel; triple-negative breast cancer