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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 volume doubling time and tumour control. A Volume doubling time (VDT) for progression or re-growth of individual tumours after irradiation with 5 × 3.3 Gy (black circles) or without irradiation (white circles) and treatment with vehicle or 40 mg/kg BW Erufosine as indicated. Horizontal lines indicate median values of the treatment groups. B Local tumour control rates and calculated tumour control probabilities after fractionated irradiation with 5 × 3.3 Gy and graded top up doses (0–30.6 Gy) combined with injection of 40 mg/kg BW Erufosine (closed red circles) or vehicle (open black triangles). Thin lines indicate 95%-confidence intervals, size of symbols reflects number of animals (n=5-21).
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Figure 5: Effect of combination treatment on volume doubling time and tumour control. A Volume doubling time (VDT) for progression or re-growth of individual tumours after irradiation with 5 × 3.3 Gy (black circles) or without irradiation (white circles) and treatment with vehicle or 40 mg/kg BW Erufosine as indicated. Horizontal lines indicate median values of the treatment groups. B Local tumour control rates and calculated tumour control probabilities after fractionated irradiation with 5 × 3.3 Gy and graded top up doses (0–30.6 Gy) combined with injection of 40 mg/kg BW Erufosine (closed red circles) or vehicle (open black triangles). Thin lines indicate 95%-confidence intervals, size of symbols reflects number of animals (n=5-21).

Mentions: In contrast, considering the volume doubling times of re-growing tumours, no significant differences were found when treated tumours with transiently decreased growth were compared with untreated continuously growing controls. In fact, the median volume doubling times were 6.0 (95% CI: 3.7;8.2), 6.6 (4.9;8.3), 9.2 (4.4; 21.0) and 8.6 (6.3;13.5) days for untreated controls, Erufosine alone, fractionated irradiation alone and combination therapy, respectively (Figure 5A).


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 volume doubling time and tumour control. A Volume doubling time (VDT) for progression or re-growth of individual tumours after irradiation with 5 × 3.3 Gy (black circles) or without irradiation (white circles) and treatment with vehicle or 40 mg/kg BW Erufosine as indicated. Horizontal lines indicate median values of the treatment groups. B Local tumour control rates and calculated tumour control probabilities after fractionated irradiation with 5 × 3.3 Gy and graded top up doses (0–30.6 Gy) combined with injection of 40 mg/kg BW Erufosine (closed red circles) or vehicle (open black triangles). Thin lines indicate 95%-confidence intervals, size of symbols reflects number of animals (n=5-21).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Effect of combination treatment on volume doubling time and tumour control. A Volume doubling time (VDT) for progression or re-growth of individual tumours after irradiation with 5 × 3.3 Gy (black circles) or without irradiation (white circles) and treatment with vehicle or 40 mg/kg BW Erufosine as indicated. Horizontal lines indicate median values of the treatment groups. B Local tumour control rates and calculated tumour control probabilities after fractionated irradiation with 5 × 3.3 Gy and graded top up doses (0–30.6 Gy) combined with injection of 40 mg/kg BW Erufosine (closed red circles) or vehicle (open black triangles). Thin lines indicate 95%-confidence intervals, size of symbols reflects number of animals (n=5-21).
Mentions: In contrast, considering the volume doubling times of re-growing tumours, no significant differences were found when treated tumours with transiently decreased growth were compared with untreated continuously growing controls. In fact, the median volume doubling times were 6.0 (95% CI: 3.7;8.2), 6.6 (4.9;8.3), 9.2 (4.4; 21.0) and 8.6 (6.3;13.5) days for untreated controls, Erufosine alone, fractionated irradiation alone and combination therapy, respectively (Figure 5A).

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