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

• Published in: Radiation oncology (London, England) Vol. 7; no. 1; p. 172
• Main Authors: Henke, Guido, Meier, Verena, Lindner, Lars H, Eibl, Hansjörg, Bamberg, Michael, Belka, Claus, Budach, Wilfried, Jendrossek, Verena
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18-10-2012; BioMed Central; BMC
• Subjects: Analysis; Animals; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Apoptosis; Aqueous solutions; Blood-brain barrier; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Brain Neoplasms - radiotherapy; Brain tumors; Cancer; Cancer therapies; Care and treatment; Chemoradiotherapy - methods; Chemotherapy; Combination therapy; Erufosine; Experiments; Glioblastoma - drug therapy; Glioblastoma - pathology; Glioblastoma - radiotherapy; Glioblastoma multiforme; Humans; Ionizing radiation; Kinases; Local control; Magnetic resonance imaging; Mice; Mice, Nude; Mouse model; Organophosphates - administration & dosage; Organophosphates - pharmacokinetics; Quaternary Ammonium Compounds - administration & dosage; Quaternary Ammonium Compounds - pharmacokinetics; Radiation therapy; Radiotherapy; Radiotherapy - methods; Signal transduction; T98G glioblastoma; Tissue Distribution; Tumors; Xenograft Model Antitumor Assays; Xenograft tumours; United Kingdom
• ISSN: 1748-717X; 1748-717X
• DOI: 10.1186/1748-717X-7-172

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.
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.
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.
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.