Low-Dose Sorafenib May Improve Cancer Therapy
Researchers at Ohio State University’s Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) discovered adding low doses of targeted agent, sorafenib, to chemotherapy and radiation might significantly improve patient care and quality of life for those with head and neck cancer.
The findings suggest sorafenib would maintain treatment efficiency while permitting the use of lower doses of chemotherapy and radiation and decreasing the treatment’s harsh side effects. The triple combination was well-tolerated in an animal model.
“This pre-clinical study suggests that using low-dose sorafenib along with chemotherapy and radiation could have significantly milder side effects while maintaining effectiveness,” says researcher and principal investigator Pawan Kumar, PhD, assistant professor of otolaryngology and a neck surgeon at the OSUCCC – James.
“Our findings provide a scientific rationale to evaluate this combination strategy through a clinical trial,” Kumar added.
The results of the laboratory and animal study are published online in Molecular Cancer Therapeutics, and showed sorafenib sensitized tumor cells react to chemotherapy and radiation by down-regulating DNA repair proteins (ERCC-1 and XRCC-1). It decreased tumor angiogenesis by inhibiting VEGF-mediated signaling. The combination treatment was well tolerated in a mouse model and significantly inhibited tumor growth and tumor angiogenesis; low-dose sorafenib alone was an effective maintenance regimen. The combination treatment significantly inhibited tumor-cell migration, invasion, and the formation of new tumor blood vessels in laboratory studies.
“Taken together, our results suggest a potentially novel strategy in which sorafenib combined with low doses of chemotherapy, radiation therapy, or both is as effective in the treatment of head and neck cancer as much higher doses used in existing treatment approaches,” says study co-author Theodoros N. Teknos, PhD, professor of otolaryngology, director of head and neck oncologic surgery, and the David E. and Carole H. Schuller chair in head and neck oncologic surgery. “As a result, it may be possible to design new treatment regimens that limit side effects of therapy without decreasing cure rates.”
Release Date: May 16, 2011
Source: The Ohio State University Comprehensive Cancer Center