Equivalency challenge: Evaluation of Lipodox® as the generic equivalent for Doxil® in a human ovarian cancer orthotropic mouse model

Gynecol Oncol. 2016 May;141(2):357-363. doi: 10.1016/j.ygyno.2016.02.033. Epub 2016 Mar 8.


Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Bioequivalence; Doxil; Doxorubicin; Lipodox; Liposomal; Microdialysis; Ovarian cancer.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / pharmacology
  • Cell Line, Tumor
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Polyethylene Glycols / pharmacokinetics
  • Polyethylene Glycols / pharmacology
  • Random Allocation
  • Therapeutic Equivalency
  • Xenograft Model Antitumor Assays


  • Antibiotics, Antineoplastic
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin