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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

Average of tumor volumes for every measurement days of the experiment in the case of Phase I, Phase III/3 control and Phase III/3 case group.The significant difference between quasi-continuous therapy (Phase III/3 case group) and tumor growth without treatment (Phase I) was proved with statistical analysis as well.
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pone.0142190.g008: Average of tumor volumes for every measurement days of the experiment in the case of Phase I, Phase III/3 control and Phase III/3 case group.The significant difference between quasi-continuous therapy (Phase III/3 case group) and tumor growth without treatment (Phase I) was proved with statistical analysis as well.

Mentions: To compare more than two samples, ANOVA test was applied. We have found that there is significant difference between the means of the samples (p = 0.002, using 0.05 level of significance). Pairwise comparison was done by Tukey’s honest significant difference test to find those samples, which have significantly different means. The post hoc test resulted in the following. Phase I and Phase III/3 control groups are not significantly different (p = 0.572), while Phase I and Phase III/3 control groups are significantly different (p = 0.002). This means that mice which were treated with the recommended bevacizumab protocol (one 200 μg bevacizumab dose for an 18-day therapy) did not have significantly smaller tumor volume than mice which did not receive therapy at all. However mice which were treated with a quasi-continuous therapy (one-tenth dose of control dose spread over 18 days, i.e. 1.11 μg bevacizumab every day) had significantly smaller tumor volume than mice that did not receive therapy. Average of tumor volumes for every measurement days of the experiment can be seen in Fig 8.


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)

Average of tumor volumes for every measurement days of the experiment in the case of Phase I, Phase III/3 control and Phase III/3 case group.The significant difference between quasi-continuous therapy (Phase III/3 case group) and tumor growth without treatment (Phase I) was proved with statistical analysis as well.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0142190.g008: Average of tumor volumes for every measurement days of the experiment in the case of Phase I, Phase III/3 control and Phase III/3 case group.The significant difference between quasi-continuous therapy (Phase III/3 case group) and tumor growth without treatment (Phase I) was proved with statistical analysis as well.
Mentions: To compare more than two samples, ANOVA test was applied. We have found that there is significant difference between the means of the samples (p = 0.002, using 0.05 level of significance). Pairwise comparison was done by Tukey’s honest significant difference test to find those samples, which have significantly different means. The post hoc test resulted in the following. Phase I and Phase III/3 control groups are not significantly different (p = 0.572), while Phase I and Phase III/3 control groups are significantly different (p = 0.002). This means that mice which were treated with the recommended bevacizumab protocol (one 200 μg bevacizumab dose for an 18-day therapy) did not have significantly smaller tumor volume than mice which did not receive therapy at all. However mice which were treated with a quasi-continuous therapy (one-tenth dose of control dose spread over 18 days, i.e. 1.11 μg bevacizumab every day) had significantly smaller tumor volume than mice that did not receive therapy. Average of tumor volumes for every measurement days of the experiment can be seen in Fig 8.

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