Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs With Spontaneously Occurring Tumors as a Model.

To evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded
minicells to deliver doxorubicin to spontaneous brain tumors in 17 companion
dogs; a comparative oncology model of human brain cancers.

EGFRminicellsDox were administered
weekly via intravenous injection to 17 dogs with late-stage brain cancers.
Biodistribution was assessed using PET and MRI. 
Anti-tumor response was determined using MRI, and blood samples were
subject to toxicology (hematology, biochemistry) and inflammatory marker
analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core
of brain tumors. Complete resolution or marked tumor regression (>90%
reduction in tumor volume) were observed in 23.53% of the cohort, with lasting
anti-tumor responses characterized by remission in three dogs for more than two
years. The median overall survival was 264 days (range 49 to 973). No adverse
clinical, hematological or biochemical effects were observed with repeated
administration of EGFRminicellsDox (30 to 98 doses
administered in 10 of the 17 dogs).