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Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice.

Henke G, Meier V, Lindner LH, Eibl H, Bamberg M, Belka C, Budach W, Jendrossek V - Radiat Oncol (2012)

Bottom Line: Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.We show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice.Further studies are needed to evaluate efficacy of extended drug treatment schedules.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiooncology, University Hospital Tübingen, Hoppe-Seyler-Str, 3, Tübingen 72076, Germany.

ABSTRACT

Background: Erufosine is a promising anticancer drug that increases the efficacy of radiotherapy in glioblastoma cell lines in vitro. Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.

Methods: In the present study we aimed to evaluate the effects of a combined treatment with radiotherapy and Erufosine on growth and local control of T98G subcutaneous glioblastoma xenograft-tumours in NMRI nu/nu mice.

Results: We show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice. Moreover, short-term treatment with 5 intraperitoneal Erufosine injections caused a transient decrease in the growth of T98G tumours without radiotherapy. Furthermore, an increased radiation-induced growth delay of T98G xenograft tumours was observed when fractionated irradiation was combined with short-term Erufosine-treatment. However, no beneficial drug effects on fractionated radiotherapy in terms of local tumour control were observed.

Conclusions: We conclude that short-term treatment with Erufosine is not sufficient to significantly improve local control in combination with radiotherapy in T98G glioblastoma xenograft tumours. Further studies are needed to evaluate efficacy of extended drug treatment schedules.

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Effect of combination treatment on tumour growth delay. A Modified growth delay to four-fold of starting volume after combined treatment. Given are Kaplan-Meier-plots of mock-irradiated tumours combined with vehicle (open black diamonds) or 40 mg/kg BW Erufosine (open red squares) and 5 × 3.3 Gy combined with vehicle (closed black diamonds) or 40 mg/kg BW Erufosine (closed red squares). B Respective computed median growth delay of data obtained in A) with 95%-confidence interval (n=14-18). C Modified growth delay to eight-fold of starting volume after combined treatment. Given are Kaplan-Meier-plots of mock- irradiated tumours combined with vehicle (open black diamonds) or 40 mg/kg BW Erufosine (open red squares) and 5 × 3.3 Gy combined with vehicle (closed black diamonds) or 40 mg/kg BW Erufosine (closed red squares). D Respective computed median growth delay of data obtained in C) with 95%-confidence interval (n=14-18).
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Figure 4: Effect of combination treatment on tumour growth delay. A Modified growth delay to four-fold of starting volume after combined treatment. Given are Kaplan-Meier-plots of mock-irradiated tumours combined with vehicle (open black diamonds) or 40 mg/kg BW Erufosine (open red squares) and 5 × 3.3 Gy combined with vehicle (closed black diamonds) or 40 mg/kg BW Erufosine (closed red squares). B Respective computed median growth delay of data obtained in A) with 95%-confidence interval (n=14-18). C Modified growth delay to eight-fold of starting volume after combined treatment. Given are Kaplan-Meier-plots of mock- irradiated tumours combined with vehicle (open black diamonds) or 40 mg/kg BW Erufosine (open red squares) and 5 × 3.3 Gy combined with vehicle (closed black diamonds) or 40 mg/kg BW Erufosine (closed red squares). D Respective computed median growth delay of data obtained in C) with 95%-confidence interval (n=14-18).

Mentions: In line with these results, the median growth delay until completion of the 4- and 8-fold initial tumour volume significantly increased after fractionated irradiation. Again, laying emphasis on the early observation period, a trend (Wilcoxon-Test p=0.08) to an increased tumour growth delay was observed when Erufosine treatment was used in combination with fractionated irradiation (Figure 4). The respective growth delay to 4- and 8-fold initial tumour volumes upon Erufosine-treatment amounted to 14 and 25 days compared to 15 and 27 days in the untreated controls without irradiation and 82 and 105 days compared to 63 and 94 days in the controls with irradiation.


Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice.

Henke G, Meier V, Lindner LH, Eibl H, Bamberg M, Belka C, Budach W, Jendrossek V - Radiat Oncol (2012)

Effect of combination treatment on tumour growth delay. A Modified growth delay to four-fold of starting volume after combined treatment. Given are Kaplan-Meier-plots of mock-irradiated tumours combined with vehicle (open black diamonds) or 40 mg/kg BW Erufosine (open red squares) and 5 × 3.3 Gy combined with vehicle (closed black diamonds) or 40 mg/kg BW Erufosine (closed red squares). B Respective computed median growth delay of data obtained in A) with 95%-confidence interval (n=14-18). C Modified growth delay to eight-fold of starting volume after combined treatment. Given are Kaplan-Meier-plots of mock- irradiated tumours combined with vehicle (open black diamonds) or 40 mg/kg BW Erufosine (open red squares) and 5 × 3.3 Gy combined with vehicle (closed black diamonds) or 40 mg/kg BW Erufosine (closed red squares). D Respective computed median growth delay of data obtained in C) with 95%-confidence interval (n=14-18).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539870&req=5

Figure 4: Effect of combination treatment on tumour growth delay. A Modified growth delay to four-fold of starting volume after combined treatment. Given are Kaplan-Meier-plots of mock-irradiated tumours combined with vehicle (open black diamonds) or 40 mg/kg BW Erufosine (open red squares) and 5 × 3.3 Gy combined with vehicle (closed black diamonds) or 40 mg/kg BW Erufosine (closed red squares). B Respective computed median growth delay of data obtained in A) with 95%-confidence interval (n=14-18). C Modified growth delay to eight-fold of starting volume after combined treatment. Given are Kaplan-Meier-plots of mock- irradiated tumours combined with vehicle (open black diamonds) or 40 mg/kg BW Erufosine (open red squares) and 5 × 3.3 Gy combined with vehicle (closed black diamonds) or 40 mg/kg BW Erufosine (closed red squares). D Respective computed median growth delay of data obtained in C) with 95%-confidence interval (n=14-18).
Mentions: In line with these results, the median growth delay until completion of the 4- and 8-fold initial tumour volume significantly increased after fractionated irradiation. Again, laying emphasis on the early observation period, a trend (Wilcoxon-Test p=0.08) to an increased tumour growth delay was observed when Erufosine treatment was used in combination with fractionated irradiation (Figure 4). The respective growth delay to 4- and 8-fold initial tumour volumes upon Erufosine-treatment amounted to 14 and 25 days compared to 15 and 27 days in the untreated controls without irradiation and 82 and 105 days compared to 63 and 94 days in the controls with irradiation.

Bottom Line: Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.We show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice.Further studies are needed to evaluate efficacy of extended drug treatment schedules.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiooncology, University Hospital Tübingen, Hoppe-Seyler-Str, 3, Tübingen 72076, Germany.

ABSTRACT

Background: Erufosine is a promising anticancer drug that increases the efficacy of radiotherapy in glioblastoma cell lines in vitro. Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.

Methods: In the present study we aimed to evaluate the effects of a combined treatment with radiotherapy and Erufosine on growth and local control of T98G subcutaneous glioblastoma xenograft-tumours in NMRI nu/nu mice.

Results: We show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice. Moreover, short-term treatment with 5 intraperitoneal Erufosine injections caused a transient decrease in the growth of T98G tumours without radiotherapy. Furthermore, an increased radiation-induced growth delay of T98G xenograft tumours was observed when fractionated irradiation was combined with short-term Erufosine-treatment. However, no beneficial drug effects on fractionated radiotherapy in terms of local tumour control were observed.

Conclusions: We conclude that short-term treatment with Erufosine is not sufficient to significantly improve local control in combination with radiotherapy in T98G glioblastoma xenograft tumours. Further studies are needed to evaluate efficacy of extended drug treatment schedules.

Show MeSH
Related in: MedlinePlus