Low-dose sorafenib may improve therapy for head and neck cancer

Dr. Pawan Kumar: “Our findings provide a scientific rationale to evaluate this combination strategy through a clinical trial."

The findings suggest that adding sorafenib would maintain treatment efficacy 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.

About 49 200 new cases of head and neck cancer are expected in the US this year, and 11 500 people are expected to die of the disease. Treatment is often unsuccessful because the tumours become resistant to both chemotherapy and radiation therapy.

'Significantly milder side-effects'

"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 Dr. Pawan Kumar, assistant professor of otolaryngology and head and neck surgery 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 the journal Molecular Cancer Therapeutics, and they include the following:

• Sorafenib sensitised tumour cells to chemotherapy and radiation treatment by down-regulating DNA repair proteins (ERCC-1 and XRCC-1), and it decreased tumour angiogenesis by inhibiting VEGF-mediated signalling.
  
• The combination treatment was well tolerated in a mouse model and significantly inhibited tumour growth and tumour angiogenesis; low-dose sorafenib alone was an effective maintenance regimen.
  
• The combination treatment significantly inhibited tumour-cell migration, invasion and the formation of new tumour 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 Dr. Theodoros N. Teknos, 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."

Funding from the National Cancer Institute and Joan's Fund supported this research.

Other Ohio State researchers involved in this study were Arti Yadav and Bhavna Kumar.

The Ohio State University Comprehensive Cancer Centre - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (http://cancer.osu.edu) is one of only 40 Comprehensive Cancer Centres in the United States designated by the National Cancer Institute. Ranked by US News & World Report among the top cancer hospitals in the nation, The James is the 205-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven programs in the country funded by the NCI to conduct both Phase I and Phase II clinical trials.

Source: Ohio State University