gms | German Medical Science

Objective: The anti-glioma efficacy of TMZ is hampered by the rapid development of tumor cell drug resistance. For these tumors, the metronomic scheduling of TMZ has been suggested as an anti-angiogenic strategy. However, so far evidence for an anti-angiogenic efficacy of metronomic TMZ is lacking. Therefore, the aim of the present study was to evaluate the consequences of metronomic TMZ on experimental glioma vascularization.

Methods: We used the human glioma cell lines SF188wt (TMZ sensitive) and SF188TR (TMZ resistant). 5x105 cells of each SF188 clone were implanted into the dorsal skinfold chamber of nude mice. Animals received TMZ as a metronomic scheduling (20mg/m² daily, i.p.), starting on day 1 after implantation. A vehicle treated group served as control. Tumor angiogenesis, tumor perfusion and angioarchitecture were repeatedly assessed by intravital fluorescence videomicroscopy over an observation period of 21 days.

Results: All animals tolerated the daily metronomic scheduling of TMZ well. Metronomic scheduling of TMZ resulted in a 44% inhibition of tumor growth. However, intravital microscopy revealed that the metronomic scheduling of TMZ exerted only a moderate anti-angiogenic efficacy when given over 21 days, with a reduction in tumor blood vessel density by 16% and 20% for SF188wt and SF188TR cells, respectively.

Conclusions: The metronomic scheduling of TMZ exerts both anti-tumor and anti-angiogenic efficacies in mice. However, with respect to its only moderate effect on tumor angiogenesis, a combination with additional anti-angiogenic compounds should be considered for a future clinical application.