An estimated 400,000 U.S. patients undergoing chemotherapy and radiation therapy each year develop painful mouth sores known as oral mucositis. Researchers across UConn are attacking this common side effect from several angles, with one team working to understand the root causes of the ulcers and another developing a better way to treat them.
Cancer drugs break down the mucous membranes lining the mouth, called oral mucosa, inducing painful lesions that can cause difficulty talking, swallowing, and eating. The pain can become so severe that patients require feeding intravenously or through a stomach tube. Other risks to patients include slower healing, decreased resistance to infection, and general failure to thrive. Secondary infection and potentially life-threatening systemic sepsis have also 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.
One UConn School of Dental Medicine research team published in Springer Nature’s Microbiome the most comprehensive study to date about the patho-physiology of oral mucositis in humans due to the effects of chemotherapy.
The team, led by Dr. Patricia Diaz, associate professor in the Department of Oral Health and Diagnostic Sciences, found that patients who developed the most severe lesions showed suppression of beneficial mouth bacteria and outgrowth of harmful ones.
Further studies are needed to understand which specific microbiome components are detrimental and in what manner they affect the oral mucosa’s ability to withstand a chemotherapy challenge.
Meanwhile, Dr. Rajesh Lalla, professor of dental medicine, is collaborating with UConn Board of Trustees Distinguished Professor of Pharmaceutical Sciences Diane J. Burgess, graduate student Tingting Li, and drug design firm Cellix Bio to develop a new, long-acting topical anesthetic that he hopes will someday replace current methods of treating oral mucositis.
The current first-line therapy at most U.S. hospitals is a mouth rinse containing the local anesthetic lidocaine, providing about 30 minutes of relief. The rinse numbs the entire mouth instead of focusing specifically on the sores, which poses safety concerns since it can inhibit the swallowing reflex. Patients are also often prescribed systemic opioids to treat the pain.
The team has developed an innovative formulation and novel patented compound that allows a long-acting topical anesthetic to be applied directly to sores. The researchers expect the more potent anesthetic should relieve pain for about four hours, eight times as long as the standard mouth rinse.
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, says Lalla.
Lalla and his collaborators believe they are one to two years away from clinical trials in humans.