Chapel Hill -- Breast cancer brain metastases present a challenge to clinicians because there are few systemic therapies capable of crossing the blood-brain barrier to control the disease. An international team, led by scientists at the University of North Carolina Lineberger Comprehensive Cancer Center, reports pre-clinical research showing improved efficacy of a PEGylated liposomal (encapsulated) anti-cancer agent compared with a non-liposomal formulation of the same drug in an intracranial model of breast cancer.
The study results were published online in the May 1, 2013 issue of PLOS ONE.
Carey Anders, MD, assistant professor of medicine and study first author, says, "To our knowledge this study is the first of its kind in brain cancer metastases and offers an informed foundation for the development of early-phase clinical trials. It also offers the potential to improve the current treatment paradigm for patients with intracranial breast cancer recurrence." Dr. Anders is co-director of the UNC Multidisciplinary Brain Metastases Specialty Clinic.
In this study, the scientists used an intracranial model of aggressive triple negative breast cancer to evaluate the pharmacokinetics of a chemotherapy drug, anthracycline doxorubicin in a PEGYlated liposomal-formulation, compared to a non-liposomal formulation. They augmented the liposomal doxorubicin with ABT-888, an inhibitor of an enzyme involved in many cellular functions, called poly (ADP-ribose) polymerase (PARP).
Their results showed that treatment with PEGylated liposomal doxorubicin resulted in a 1500-fold higher plasma and 20-fold higher intracranial tumor bioavailability compared with the non-liposomal doxorubicin. In addition, PEGylated liposomal doxorubicin was detected in in plasma and the intracranial tumor 96 hours following treatment compared to the drug being undetectable in plasma and the tumor after 24 hours in the non-liposomal doxorubicin. Survival rates for the PEGylated liposomal doxorubicin treatment were significantly prolonged as compared to non-liposomal doxorubicin.
UNC authors are: Olga Karginova, MS; Allison Deal, MS; Sumit Rawal, PhD; David Darr, MS; Allison Schorzman, PhD; Charlene Santos, BS; Ryan Bash, MS; Tal Kafri, PhD; Lisa Carey, MD; C. Ryan Miller, MD, PhD; Charles Perou, PhD; Norman Sharpless, MD; and William Zamboni, PharmD, PhD. Barbara Adamo, PhD, is affiliated with UNC and with the University of Messina, Italy.
The research was funded by the National Cancer Institute (K23 and Specialized Program of Research Excellence in Breast Cancer SPORE) and the Breast Cancer Research Foundation.
- Carey K. Anders, Barbara Adamo, Olga Karginova, Allison M. Deal, Sumit Rawal, David Darr, Allison Schorzman, Charlene Santos, Ryan Bash, Tal Kafri, Lisa Carey, C. Ryan Miller, Charles M. Perou, Norman Sharpless, William C. Zamboni. Pharmacokinetics and Efficacy of PEGylated Liposomal Doxorubicin in an Intracranial Model of Breast Cancer. PLoS ONE, 2013; 8 (5): e61359 DOI: 10.1371/journal.pone.0061359
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