Researchers have found promising results from a drug combination that appears to reduce the risk for patients with advanced oral precancerous lesions to develop squamous cell carcinoma of the head and neck (SCCHN), according to a new study published in Clinical Cancer Research (February 19, 2013).
SCCHN is the most common form of head and neck cancer, and survival rates are very poor, making an effective preventive approach crucial, the researchers noted. "An effective prevention approach is desperately needed, especially since we can identify patients who are at extremely high risk: those with advanced oral precancerous lesions," stated Dong Moon Shin, MD, in a press release. Dr. Shin is a professor of hematology, medical oncology, and otolaryngology at Emory University School of Medicine and the director of the Clinical and Translational Cancer Prevention Program at Winship Cancer Institute.
Dr. Shin and colleagues examined previous research on the role of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in promoting SCCHN, and believed combining inhibitors for both could provide an effective chemopreventive approach.
They found that the combination of the EGFR inhibitor erlotinib and the COX-2 inhibitor celecoxib was more effective for inhibiting the growth of human SCCHN cell lines compared with either drug alone. In addition, treating mice with the drug combination prior to transplanting them with human SCCHN cells more effectively suppressed cancer cell growth than did pretreating the mice with either drug alone.
After their preclinical analyses, the researchers initiated a phase I chemoprevention trial. The study included 11 patients who had advanced oral precancerous lesions, all of whom were treated with the inhibitor combination. At three, six, and 12 months of therapy, tissue samples were evaluated pathologically. Baseline biopsy and follow-up data were available for seven patients. The researchers found no evidence of precancerous lesions in the follow-up biopsies in three patients, partial pathologic responses occurred in two, and disease progressed in the remaining two.
Several patients dropped out of the trial because of severe adverse side effects. "So, we need to investigate the safety and toxicity of this combination further before planning a large-scale trial," Dr. Shin stated. "We are also looking to combination therapies using less toxic or nontoxic agents, such as natural compounds."