Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy

PLoS One. 2015 Nov 5;10(11):e0142190. doi: 10.1371/journal.pone.0142190. eCollection 2015.

Abstract

Background: Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol.

Materials and methods: We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis.

Results: In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model.

Conclusion: Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology*
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Bevacizumab / pharmacology*
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology*
  • Disease Models, Animal
  • HT29 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Non-Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Tumor Burden / drug effects*

Substances

  • Angiogenesis Inhibitors
  • Bevacizumab

Grants and funding

This work was supported by Hungarian Scientific Research Fund (OTKA), http://www.otka.hu/en, No: K-112993 (János) and Bolyai Research Scholarship of the Hungarian Academy of Sciences, http://mta.hu/cikkek/?node_id=26057, No: 425_12. Coauthors PK and DG are employed by Gedeon Richter Ltd. Gedeon Richter Ltd. provided support in the form of salaries for authors PK and DG, and in the form of using the resources of Preclinical Imaging Center of Gedeon Richter Ltd., but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the “author contributions” section.