title: Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy.
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.
  
  
  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.
  
  
  CONCLUSIONS
  Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration.
authors.affiliation: Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary.
authors.forename: Johanna
authors.initials: J
authors.lastname: Sápi
authors.affiliation: Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Kovács
authors.affiliation: Department of Control Engineering and Information Technology, Budapest University of Technology and Economics, Budapest, Hungary.
authors.forename: Dániel András
authors.initials: DA
authors.lastname: Drexler
authors.affiliation: Preclinical Imaging Center, Gedeon Richter Plc., Budapest, Hungary.
authors.forename: Pál
authors.initials: P
authors.lastname: Kocsis
authors.affiliation: Preclinical Imaging Center, Gedeon Richter Plc., Budapest, Hungary.
authors.forename: Dávid
authors.initials: D
authors.lastname: Gajári
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Sápi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000068258:Bevacizumab / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065228:Non-Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab