NEO 212 Study Shows Increased Efficacy For Treatment Of Brain Metastasized Breast Cancer
A Novel Temozolomide-Perillyl Alcohol Conjugate Exhibits Superior Activity Against Breast Cancer Cells In Vitro And Intracranial Triple-Negative Tumor Growth In Vivo
Authors: Thomas C Chen1,2, Hee-Yeon Cho2, Weijun Wang1, Manasi Barath3, Natasha Sharma4, Florence M. Hofman2, Axel H. Schönthal3
A study was conducted to determine the ability of NEO 212, a conjugate formulation of Temozolomide (TMZ) and Peryllil Alcohol (POH), to have increased efficacy in helping to treat breast cancer cells that had metastasized to the brain.
Currently, there is no effective therapy for breast cancer that has spread to the brain. A major roadblock is the blood-brain-barrier (BBB), which prevents the usual breast cancer drugs from effectively reaching intracranial metastases. The alkylating agent temozolomide (TMZ) is able to penetrate the BBB and has become the gold standard for the chemotherapeutic treatment of glioblastoma. However, when it was tested in clinical trials for activity against brain metastases of breast cancer, the results were mixed and ranged from “encouraging activity” to “no objective responses.” This study was conducted to determine if conjugates TMZ POH would provide greater therapeutic efficacy than TMZ alone.
Both the in vivo and in vitro studies showed that the NEO 212 TMZ POH conjugate showed greater effect and provided longer survivability that TMZ alone or TMZ simply mixed with POH. Median survival rates went from 36 days for TMZ treated only animals to 80 days for NEO 212 treated animals. Indeed, where a single cycle of treatment extended median survival benefit from 6 days (in the case of TMZ) to 28 days. At the same time, NEO 212 appeared to be well tolerated by the animals. Thus, NEO 212 may have potential as a novel therapy for brain-targeted breast cancer metastases.
1 Department of Neurosurgery, University of Southern California, Los Angeles, California, USA, 2 Department of Pathology, University of Southern California, Los Angeles, California, USA, 3 Department of Molecular Microbiology and
Immunology, University of Southern California, Los Angeles, California, USA, 4Department of 4Pharmaceutical Sciences, University of Southern California, Los Angeles, California, USA,