HER2 Support Group Forums - new brain tumor treatment ? for mets, too if proves itself

2069 General Poster Session (Board #15H), Sat, 1:15 PM-5:15 PM
Effect of electrochemotherapy with IV bleomycin on complete response in a preclinical brain tumor study.
Birgit Agerholm-Larsen, Helle K. Iversen, Jakob M. Moller, Per Ibsen, Kurt S. Jensen, Mette Linnert, Julie Gehl; Department of Oncology, C*EDGE at Glostrup Research Institue, Glostrup, Denmark; Department of Neurology, C*EDGE at Glostrup Research Institute, Copenhagen University Hospital Glostrup, Glostrup, Denmark; Department of Radiology, Copenhagen University Hospital Herlev, Herlev, Denmark; Department of Pathology, Copenhagen University Hospitals Herlev and Hvidovre, Hvidovre, Denmark; Department of Oncology, C*EDGE at Glostrup Research Institute, Glostrup, Denmark; Center for Experimental Drug and Gene Electrotransfer (C*EDGE), Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark
Background: Electrochemotherapy (ECT) describes enhanced chemotherapeutic drug uptake after cell membranes have been made transiently permeable due to application of an electric field to the tumor. ECT is routinely used to treat skin metastases, with high response rates after once-only treatment. We have developed an electrode for use in the brain, both a rodent model and an electrode for clinical use. The aim of the present study was to evaluate ECT using intravenous (iv) bleomycin in a rat brain tumor model. Methods: Sprague Dawley male rats (7-11 week old) were inoculated with rat glial cell derived tumor cells (N32) through a burr hole in the skull. When tumors appeared on MRI, animals were allocated to ECT (iv bleomycin and local electric pulses), iv bleomycin only, iv bleomycin with placement of electrodes (no pulses), or no treatment. Bleomycin was injected iv in the tail vein (600􏰊L, 3 IU/􏰊L) and electrode deployment was made through the burr hole into the brain tissue. Electrochemotherapy parameters were 32 pulses, 100V, 100􏰊s, 1Hz. Tumor size was determined based on contrast enhanced area from MR scans. Kaplan-Meyer events were defined as termination due to extensive tumor progression prior to end of the three independent experiments performed. Immuno-histo-pathology was performed after termination to verify MRI findings. Results: In 88% of the animals (14 of 16) treated with electrochemotherapy we found complete response (no tumor), validated by MRI and immuno-histo-pathology, whereas bleomycin only, bleomycin and electrodes, and no treatment showed progression in 11 out of 13 control animals. A Kaplan-Meier plot showed a pronounced improved survival for the ECT group as compared to controls within 3 weeks from treatment (p􏰀0.001). Treatment was well tolerated. Conclusions: The present data suggest that electrochemotherapy with iv injection of bleomycin is a new promising treatment for brain tumors. In a clinical study using iv bleomycin and electrochemotherapy for brain metastases (www.clini- caltrials.gov, ID:NCT01322100) the first patient has just been treated successfully with ECT, indicating feasibility of the approach in the clinical setting.