Researchers at the University of Connecticut are collaborating with drug design firm Cellix Bio to develop a long-acting topical anesthetic that may replace current methods for treating oral mucositis, a common and painful side effect of cancer treatment that affects nearly 400,000 people in the United States each year.
Occurring after chemotherapy and radiation therapy, oral mucositis involves intensely painful sores in the mouth that can cause difficulties in talking, swallowing, and eating. It can become so severe that patients may require feeding intravenously or through a stomach tube. Poor nutrition can then lead to other problems for people who are already immunocompromised.
In addition to weight loss, these patients also may heal more slowly, have decreased resistance to infection, and experience a general failure to thrive. Secondary infection and potentially life-threatening sepsis also have been reported.
“While the pain that oral mucositis causes is certainly of great concern, perhaps the most harmful impact occurs when patients are in such extreme agony that their attending physicians have no choice but to prescribe undesirable dose reductions or treatment breaks in cancer therapy,” said Rajesh Lalla, DDS, PhD, professor of dental medicine at UConn Health.
“It would then come as no surprise that such modifications can spell less than optimal results for treating a patient’s cancer. Finding a better way to treat oral mucositis could help clinicians and patients better battle their primary cancer diagnosis,” said Lalla.
Current first-line therapy is a mouth rinse containing lidocaine. For best results, patients swish for about two minutes to experience only about 30 minutes of relief. The rinse also numbs the entire mouth instead of focusing specifically on the oral mucositis sores, which poses safety concerns since it can inhibit the swallowing reflex.
Many patients, then, are prescribed systemic opioids to treat pain from oral mucositis, which Lalla equates to hanging a picture with a sledge hammer.
“While it might get the job done, it is probably overkill and could certainly cause unnecessary damage,” said Lalla.
With the help of Diane J. Burgess, PhD, of the UConn School of Pharmacy, Lalla and his collaborators say they are close to replacing the “sledge hammer” with a more precise and effective treatment option that doesn’t include risk of addiction or abuse.
Thanks to lab work conducted by Tingting Li, a PhD student in Burgess’ lab, the researchers have developed a formulation and patented compound that delivers co-actives, a long-lasting topical anesthetic, and a medium chain fatty acid that can be applied directly to sores with a specially designed spray nozzle. This means the medication can be targeted to lesions rather than the whole mouth, allowing relief without generalized numbness.
Starting out as a liquid, the anesthetic turns into a gel when it comes into contact with the mouth and reaches the temperature of the human body. It then can stay in place on mouth sores. Since it uses an anesthetic that is more potent than lidocaine, the researchers expect it to relieve pain for about eight times as long as the standard rinse, or about four hours.
The compound also exhibits antimicrobial and anti-inflammatory effects naturally delivered by the medium chain fatty acid, which could reduce the severity of lesions from oral mucositis, said Lalla. While the researchers believe they are about a year or two away from clinical trials in humans, they are excited about its life-changing potential.
“We knew that there was a huge unmet need, that the market was wide open, and that significant data indicated this molecule was an excellent candidate,” said Mahesh Kandula, CEO and managing director of Cellix Bio.
“We are thrilled to be collaborating with such qualified researchers like Drs. Burgess and Lalla from UConn. We are confident this partnership will lead not only to successful commercialization, but also to a better prognosis for thousands of patients undergoing treatment for cancer.”