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

Sápi J, Kovács L, Drexler DA, Kocsis P, Gajári D, Sápi Z - PLoS ONE (2015)

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

View Article: PubMed Central - PubMed

Affiliation: Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary.

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.

No MeSH data available.


Related in: MedlinePlus

Overview of Phase IV.In Phase IV, control group members received no bevacizumab. Case1 group members received one 200 μg bevacizumab dose on the 8th day, case2 group members received 1.11 μg bevacizumab from the 8th day every day for 15 days.
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pone.0142190.g002: Overview of Phase IV.In Phase IV, control group members received no bevacizumab. Case1 group members received one 200 μg bevacizumab dose on the 8th day, case2 group members received 1.11 μg bevacizumab from the 8th day every day for 15 days.

Mentions: Bevacizumab is a humanized monoclonal antibody, therefore the effectivity of bevacizumab therapy in mice is not trivial. Although there are studies which confirme that “bevacizumab is as effective as the murine anti-VEGF-R2 antibody (DC101) in mouse models” ([27, 28]), we extended our experiments and performed Phase IV, where immunocompromized (SCID) mice were used with human colorectal adenocarcinoma (HT-29) xenografts. In this phase, three groups were created. Mice in the control group received no treatment (5 mice); case1 group members (10 mice) received 10 mg per kg body weight bevacizumab in one dose; while case2 group members (10 mice) received 1/180 dose of control dose for 15 days. (Fig 2).


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

Sápi J, Kovács L, Drexler DA, Kocsis P, Gajári D, Sápi Z - PLoS ONE (2015)

Overview of Phase IV.In Phase IV, control group members received no bevacizumab. Case1 group members received one 200 μg bevacizumab dose on the 8th day, case2 group members received 1.11 μg bevacizumab from the 8th day every day for 15 days.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4635016&req=5

pone.0142190.g002: Overview of Phase IV.In Phase IV, control group members received no bevacizumab. Case1 group members received one 200 μg bevacizumab dose on the 8th day, case2 group members received 1.11 μg bevacizumab from the 8th day every day for 15 days.
Mentions: Bevacizumab is a humanized monoclonal antibody, therefore the effectivity of bevacizumab therapy in mice is not trivial. Although there are studies which confirme that “bevacizumab is as effective as the murine anti-VEGF-R2 antibody (DC101) in mouse models” ([27, 28]), we extended our experiments and performed Phase IV, where immunocompromized (SCID) mice were used with human colorectal adenocarcinoma (HT-29) xenografts. In this phase, three groups were created. Mice in the control group received no treatment (5 mice); case1 group members (10 mice) received 10 mg per kg body weight bevacizumab in one dose; while case2 group members (10 mice) received 1/180 dose of control dose for 15 days. (Fig 2).

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

View Article: PubMed Central - PubMed

Affiliation: Research and Innovation Center of Obuda University, Physiological Controls Group, Obuda University, Budapest, Hungary.

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.

No MeSH data available.


Related in: MedlinePlus