gms | German Medical Science

Objective: Despite extensive treatment options involving surgical resection as well as radio- and chemotherapy, GBM remains the most aggressive intrinsic brain tumor with a poor prognosis. The current gold standard treatment includes systemic application of the alkylating chemotherapeutic agent temozolomide (TMZ). Side effects of systemic therapy are common and limit the treatment efficacy. Local tumor treatment offers considerably higher intratumoral concentration and homogenous distribution of agents. The recent disposability of soluble TMZ offers the chance of local treatment by convection enhanced delivery.

Method: In this study we hypothesize that local, intra- and peritumoral therapy with temozolomide leads to a significant longer survival compared to systemic therapy. We investigated feasibility and safety of convection enhanced delivery (CED) in a murine brain tumor model. 3 groups of 10 male nude rats were implanted with human U87 glioma cells. One control group received no treatment. The second group was treated with i.p.l TMZ for systemic chemotherapy on day 8 after tumor implantation. The third group received stereotactic guided peritumoral administration of TMZ. Initial proof of tumor growth and follow-up controls under treatment were gained with micro-PET in vivo imaging. Animals meeting the abort criteria were perfusion fixed and histopathologically (HP) evaluated.

Results: Our results indicate a significantly longer overall survival of animals in the local treatment group compared to systemic intraperitoneal treatment and the control group. Animals of the control group died between day 22–41 after U87 cell implantation. In group two (systemic therapy), 5 out of 10 animals died within day 16–60 while five animals survived. In group three (CED), 8 out of 10 animals survived and no animal died of tumor-related causes. The untreated group showed large tumors in all HP sections. In vivo imaging showed lower tumor volumes and metabolism in the CED group compared to the systemic treatment group.

Conclusions: The preliminary results of this study implicate that local antitumor therapy with TMZ via CED is a promising treatment option in a GBM model. Treatment with local or systemically administered TMZ showed no accumulation of toxic side effects. Overall survival data suspect an impact of CED on overall-free survival. Additional studies with frequent MRI and PET-imaging as well as tissue analysis are currently performed to get more insight in the single processes of CED.