Article
Differential antitumour effects of erlotinib (TarcevaTM, OSI-774), a novel epidermal growth factor receptor tyrosine kinase inhibitor, on human glioblastoma multiforme in a heterotopic in vivo model
Differentielle Antitumor-Effekte von erlotinib (TarcevaTM, OSI-774), einem neuartigen Inhibitor der Tyrosinkinase des epidermalen Wachstumsfaktorrezeptors, auf Glioblastoma multiforme in einem heterotopischen In-vivo-Modell
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Published: | April 23, 2004 |
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Outline
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Objective
We have previously demonstrated antiproliferative and antitumourigenic effects of erlotinib, a novel EGFR tyrosine kinase inhibitor, on glioblastoma multiforme (GBM) cell lines in vitro. The aim of the current study was to evaluate a potential therapeutic effect of erlotinib on GBM in a heterotopic in vivo model.
Methods
Athymic mice bearing established, palpable tumours derived from subcutaneous inoculation of cultured G-599GM or G-750GM human GBM cells (representing secondary or primary GBM, respectively) were treated with intraperitoneal injections of erlotinib once daily (50 mg/kg body weight in 200 μl 0.5% methyl cellulose) for 18 consecutive days. Correspondingly, control animals received mock intraperitoneal injections with 200 μl 0.5% methyl cellulose only. Tumour volumes were calculated based on regular tumour measurements across three diameters.
Results
Both control tumour growth and tumour response to treatment corresponded well to the proliferative behaviour in vitro in that G-750GM tumours grew faster and exhibited relative resistance against erlotinib-mediated growth inhibition while G-599GM tumours were characterized by delayed development and progression under control conditions as well as discernible regression in response to treatment. There was no compound-related mortality during the treatment period.
Conclusions
These results support our previous in vitro-based hypothesis that erlotinib may be a promising agent especially against secondary GBM. Further studies including larger sample collectives are strongly warranted.