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Intratumoral retrograde microdialysis treatment of high-grade glioma with cisplatin

  • Original Article - Brain Tumors
  • Published:
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Abstract

Purpose

This study evaluates the application of a microdialysis technique for interstitial chemotherapy using cisplatin in high-grade glioma.

Method

An in vitro study demonstrated that cisplatin can be administered through retrograde microdialysis and defined the recovery for cisplatin. In a subsequent phase I study, 1–4 microdialysis catheters were implanted in tumor tissue, brain adjacent to tumor (BAT) tissue, and subcutaneous tissue in 10 patients with recurrent high-grade glioma. Cisplatin was administered continuously in daily doses between 0.3 and 3.9 mg for 4 to12 days. Microdialysis samples were continuously collected and analyzed for glucose metabolites, glutamate, glycerol, and cisplatin concentrations. Treatment tolerability was evaluated through clinical monitoring. Quality of life was assessed using the EORTC-QLQ-C30 questionnaire for up to 3 months after treatment.

Results

This in vitro study showed that cisplatin could be administrated with a recovery of 41–97%, depending on flowrate, type of catheter, and cisplatin concentration. During the treatment, patients were exposed to a total dose of 1.2–36.8 mg cisplatin. The concentration of cisplatin in BAT, serum, and subcutaneous tissue was close to detection level in all but two patients. A transient neurologic deterioration due to edema was commonly observed, but no systemic side effects were recorded. After onset of treatment, concentrations of glutamate and glycerol were significantly increased in tumor tissue but not in BAT, with a peak after 3 days, and consistent for the rest of the treatment. Five of the patients survived between 153 and 492 days after treatment.

Conclusion

This phase I study demonstrates that retrograde microdialysis can be used to administer cisplatin interstitially into high-grade glioma tissue. A high cytotoxicity was detected in tumor tissue, but not in the surrounding brain. Retrograde microdialysis appears to be a clinically useful method for intratumoral drug administration in high-grade glioma.

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Acknowledgements

We acknowledge Kristin Nyman at the Department of Neurosurgery for her technical skills in managing the microdialysis bedside and Professor Thomas Brännström at the Department of Pathology for verification of IDH mutation status.

Funding

This study was supported by the Swedish Cancer Society, Umeå University Hospital, the Swedish Research Council, the Cancer Research Foundation in Northern Sweden, the Research Foundation of Clinical Neuroscience, Umeå University, and by the regional agreement between Umeå University and Västerbotten County Council on the cooperation in the field of Medicine, Odontology, and Health.

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Authors and Affiliations

  1. Deparment of Clinical Sciences, Neuroscience Unit, Umeå University, 90185, Umeå, Sweden

    Pedram Tabatabaei & A. Tommy Bergenheim

  2. Department of Neurosurgery Radiation Sciences, Umeå University, Umeå, Sweden

    Thomas Asklund, Per Bergström & Mikael Johansson

  3. Departments of Oncology and Chemistry, Umeå University, Umeå, Sweden

    Erik Björn

Authors
  1. Pedram Tabatabaei
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  2. Thomas Asklund
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  3. Per Bergström
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  6. A. Tommy Bergenheim
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Correspondence to Pedram Tabatabaei.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

The study was approved by the Swedish Medical Products Agency (EU no. 2010-018281-23) and the Ethics Committee of Umeå University Medical Faculty (Ethical permission: 09-199M).

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Informed consent was obtained from all participants included in the study.

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This article is part of the Topical Collection on Brain Tumors

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Tabatabaei, P., Asklund, T., Bergström, P. et al. Intratumoral retrograde microdialysis treatment of high-grade glioma with cisplatin. Acta Neurochir 162, 3043–3053 (2020). https://doi.org/10.1007/s00701-020-04488-2

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