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

• Published in: PloS one 2015-11, Vol.10 (11), p.e0142190-e0142190
• Main Authors: Sápi, Johanna, Kovács, Levente, Drexler, Dániel András, Kocsis, Pál, Gajári, Dávid, Sápi, Zoltán
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Angiogenesis Inhibitors - pharmacology; Animals; Bevacizumab; Bevacizumab - pharmacology; Biological activity; Biological effects; Breast cancer; Cancer therapies; Cell Line, Tumor; Colon; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Diabetes; Disease Models, Animal; Drug dosages; Edema; Growth models; HT29 Cells; Humans; Immunotherapy; Laboratory animals; Magnetic resonance imaging; Male; Mathematical analysis; Mathematical models; Medical research; Mice; Mice, Inbred C57BL; Monoclonal antibodies; Non-Randomized Controlled Trials as Topic; Pancreatic cancer; Physiology; Statistical analysis; Studies; Targeted cancer therapy; Therapy; Treatment Outcome; Tumor Burden - drug effects; Tumors; Two dimensional models; Vascular endothelial growth factor; Volume measurement
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0142190

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