Introduction: Cisplatin has shown to be one of the most active anticancer agents and is widely used for treatment of different solid tumour. Studies suggest that Cisplatin has a beneficial effect in the treatment of experimental brain tumours. However, the inability to pass the BBB as well as significant systemic toxicity has limited its clinical application. In our study, we have by using microdialysis technique been able to administer Cisplatin locally into the tumor and hence bypassed the systemic toxicity. In this pilote study we are investigating potentially therapeutic doses of Cisplatin and the toxicity when using this technique.
Methods: Two to three microdialysis catheters were inplanted into tumoral tissue and one in normal brain using a stereotactic technique and with known distances between the catheters. Cisplatin was administered at a concentration of 1 mg/mL in one of the catheters while sampling of microdialysate was done through the other catheter(s), and hence, the distribution of cisplatin in tissue could be measured. The flow rates of the catheters were 0.5 to 2.0 uL/min. Cisplatin was analysed by inductively coupled plasma mass spectrometry (ICPMS).
Results: By assessing the concentration of Cisplatin in the microdialysate from the drug-delivering catheters we found that 50 – 90 % of the drug in the perfusion fluid was administred into tumour tissue. A total of 1-2 mg of Cisplatin was delivered daily. The drug delivery is mainly dependent on two factors, the concentration of Cisplatin in the microdialysate and the flow rate of the perfusion in the catheters. The concentration of Cisplatin in tumour tissue decreased with distance. At 10 mm distance from the administrating catheter, doses of 1 mg/day could be measured. No or very low concentration was found in normal tissue outside the contrast enhancing tumour.
Conclusions: Microdialysis is a feasible technique for intratumoral administration of cisplatin in glioblastoma. The tissue concentration of Cisplatin needed for clinical antitumoural effect is unknown. However, our finding of a penetrance of 10-15 mm, indicates that several catheters will be needed to administer the drug into larger tumour volumes.
Patient Care: By improving our understanding of how Cisplatin is distributed in brain tissue, hopefully we can design more effective treatment modalities in the future and hence improve patient care.
Learning Objectives: Better understanding about how Cisplatin is distributed in brain tissue when administered through microdialysis catheters.