Novel Rinse to Treat Oral Candidiasis in Cancer Patients

DESCRIPTION (provided by applicant): Oral candidiasis (oropharyngeal candidosis or thrush) is a common infection in immunosuppressed individuals, and, if not blunted, can transit to esophageal candidosis or life-threatening candidemia. These potentially life-threatening fungal infections originate from the endogenous flora of the individual. For cancer patients, radiation therapy or chemotherapy further suppresses the immune system and causes the patient to become more susceptible to oral candidiasis and/or systemic fungal infections (fungemia, a fungal infection disseminated by the blood). Oral candidiasis is generally treated with systemic antifungals or oral rinses. Fluconazole tablets and clotrimazole troches are the most popular therapies. Fluconazole is indicated for use for the treatment of oral candidiasis with a single daily dose for two weeks. However, certain Candida organisms in biofilms have a dramatically reduced susceptibility to antifungal drugs including Fluconazole. Furthermore, side effects of Fluconazole include nausea, vomiting, abdominal pain, headaches, dizziness, drowsiness, fever, diarrhea, rash and changes in the sense of taste. The most serious effect is liver toxicity but this usually reverses after treatment when the drug is stopped. Nonetheless, the scope and severity of the side effects can cause some patients not to be compliant with their prescribed drug regimen. Clotrimazole is used 4 to 5 times daily for 1 to 2 weeks. Its side effects include an altered sense of taste, nausea, and an upset stomach. Once again, patient compliance with the prescribed drug regimen can be an issue not only because of the side effects but also because the patient must take 4 to 5 doses daily. The goal of this project is to develop a safe effective mouthwash without side effects to treat oral candidiasis in head and neck cancer patients. The Specific Aims include implementing current Good Manufacturing Practices (cGMP) including long-term stability studies, filing an Investigational New Drug application with the FDA, and conducting clinical efficacy trials in cancer patients to demonstrate efficacy. Candida spp. exist in 40-80% of normal individuals in the mouth, intestines, and vagina. However, Candida spp. are extremely opportunistic and if immune systems are compromised and the environment changes, Candida spp. can begin to rapidly multiply resulting in candidiasis and engender a potentially deadly disease. Given the large numbers of cancer patients worldwide, coupled with other high risk immuno- compromised individuals such as patients infected with HIV, along with the growing number of patients with xerostomia (dry mouth), a safe effective mouth rinse without side effects could have profound public health benefits.