title: Bioequivalence of Liposome-Entrapped Paclitaxel Easy-To-Use (LEP-ETU) formulation and paclitaxel in polyethoxylated castor oil: a randomized, two-period crossover study in patients with advanced cancer.
abstract: BACKGROUND
  Preclinical studies comparing paclitaxel formulated with polyethoxylated castor oil with the sonicated formulation of liposome-entrapped paclitaxel (LEP) have demonstrated that LEP was associated with reduced toxicity while maintaining similar efficacy. Preliminary studies on the pharmacokinetics in patients support earlier preclinical data, which suggested that the LEP Easy-to-Use (LEP-ETU) formulation and paclitaxel formulated with castor oil may have comparable pharmacokinetic properties.
  
  
  OBJECTIVE
  Our objectives were: (1) to determine bioequivalence of paclitaxel pharmaceutically formulated as LEP-ETU (test) and paclitaxel formulated with castor oil (reference); and (2) to assess the tolerability of LEP-ETU following intravenous administration.
  
  
  METHODS
  Patients with advanced cancer were studied in a randomized, 2-period crossover bioequivalence study. Patients received paclitaxel 175 mg/m(2) administered as an intravenous infusion over 180 minutes, either as a single-treatment cycle of the test formulation followed by a single-treatment cycle of the reference formulation, or vice versa.
  
  
  RESULTS
  Thirty-two of 58 patients were evaluable and were included in the analysis for bioequivalence. Mean total paclitaxel Cmax values for the test and reference formulations were 4955.0 and 5108.8 ng/mL, respectively. Corresponding AUC0-∞ values were 15,853.8 and 18,550.8 ng·h/mL, respectively. Treatment ratios of the geometric means were 97% (90% CI, 91%-103%) for Cmax and 84% (90% CI, 80%-90%) for AUC0-∞. These results met the required 80% to 125% bioequivalence criteria. The most frequently reported adverse events after LEP-ETU administration were fatigue, alopecia, and myalgia.
  
  
  CONCLUSIONS
  At the studied dose regimen, LEP-ETU showed bioequivalence with paclitaxel formulated with polyethoxylated castor oil.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: m.slingerland@lumc.nl.
authors.forename: Marije
authors.initials: M
authors.lastname: Slingerland
authors.affiliation: Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
authors.affiliation: Department of Pharmacy & Pharmacology, Slotervaart Hospital and The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Hilde
authors.initials: H
authors.lastname: Rosing
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Max E
authors.initials: ME
authors.lastname: Scheulen
authors.affiliation: Department of Oncology, Catharina Hospital, Eindhoven, The Netherlands.
authors.forename: Laurence J C
authors.initials: LJ
authors.lastname: van Warmerdam
authors.affiliation: Department of Pharmacy & Pharmacology, Slotervaart Hospital and The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D002368:Castor Oil / Q000031:analogs & derivatives; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D012997:Solvents; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D012997:Solvents; C023040:polyethoxylated castor oil; D002368:Castor Oil; D017239:Paclitaxel
keywords: LEP-ETU; Taxol; cancer; liposome; paclitaxel