title: Equivalency challenge: Evaluation of Lipodox® as the generic equivalent for Doxil® in a human ovarian cancer orthotropic mouse model.
abstract: The objective of this study was to evaluate the in vivo growth inhibition activity and tumor distribution of Doxil® compared to Lipodox® as its generic (GLD) in human ovarian cancer orthotopic mouse model.
  
  
  
  In the efficacy study 50 mice were randomized to: vehicle, Doxil® 5mg/kg or 10mg/kg, or GLD 5mg/kg or 10mg/kg for a total of three cycles with monitoring for response and toxicity with 10 mice in each arm. In the microdialysis(MD) study, 60 mice were randomized to: Doxil® 5mg/kg or 10mg/kg, or GLD 5mg/kg or 10mg/kg single dose (n=15 mice/arm). MD sample time points included total of 29 samples from baseline through 100h and were evaluated with a validated PaperSpray LC/MS assay.
  
  
  
  There was 15.7% decrease (p<0.0001) in efficacy of GLD the 5mg/kg and 21.3% decrease (p<0.0001) in efficacy of the 10mg/kg dose of GLD when compared to equivalent doses of Doxil®. The intratumoral concentration for the GLD ranged from 1.0 to 25.5ng/mL (5mg/kg) and 2.9-35.6ng/mL (10mg/kg) compared to 2.7-42.2ng/mL (p<0.04, 5mg/kg) and 2.0-76ng/mL (p<0.02, 10mg/kg) for the Doxil®, respectively.
  
  
  
  Significant differences in preclinical efficacy were observed between Doxil® and GLD. These may be due to significant pharmacodynamic effects of drug distribution and decrease uptake of GLD in tumor tissue. A prospective clinical comparison of these two products is warranted to determine equivalency.
authors.affiliation: Department of Gynecology, Obstetrics & Reproductive Sciences, University of Texas Health Science Center Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA; Department of Pharmacy, UTHealth-Memorial Hermann Hospital Cancer Center, 6400 Fannin Street, Suite 2900,Houston, TX 77030, USA. Electronic address: Judith.Ann.Smith@uth.tmc.edu.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Smith
authors.affiliation: Department of Gynecology, Obstetrics & Reproductive Sciences, University of Texas Health Science Center Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Lata
authors.initials: L
authors.lastname: Mathew
authors.affiliation: Department of Gynecology, Obstetrics & Reproductive Sciences, University of Texas Health Science Center Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Maryam
authors.initials: M
authors.lastname: Burney
authors.affiliation: Department of Gynecology, Obstetrics & Reproductive Sciences, University of Texas Health Science Center Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Pranavanand
authors.initials: P
authors.lastname: Nyshadham
authors.affiliation: Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1144 Pressler St, Houston, TX 77030, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology; D011897:Random Allocation; D013810:Therapeutic Equivalency; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Bioequivalence; Doxil; Doxorubicin; Lipodox; Liposomal; Microdialysis; Ovarian cancer