Novel Rinse to Treat Oral Candidiasis in Cancer Patients

治疗癌症患者口腔念珠菌病的新型漱口水

• 批准号: 7221123
• 负责人: BAKUL M BHATT
• 金额: $ 39.33万
• 依托单位: BIOMEDICAL DEVELOPMENT CORPORATION
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-02 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7221123
• 关键词: Candida; biofilm; candidiasis; clinical research; fluconazole; head; head /neck neoplasm; neoplasm /cancer

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.

描述（由申请人提供）：口腔念珠菌病（口咽念珠菌病或鹅口疮）是免疫抑制个体的常见感染，如果不加以抑制，可能会转变为食管念珠菌病或危及生命的念珠菌血症。这些可能危及生命的真菌感染源自个体的内源性菌群。对于癌症患者，放疗或化疗会进一步抑制免疫系统，导致患者更容易患口腔念珠菌病和/或全身真菌感染（真菌血症，一种通过血液传播的真菌感染）。口腔念珠菌病通常用全身抗真菌药或口腔冲洗剂治疗。氟康唑片剂和克霉唑锭剂是最流行的疗法。氟康唑适用于治疗口腔念珠菌病，每日一次，持续两周。然而，生物膜中的某些念珠菌生物体对包括氟康唑在内的抗真菌药物的敏感性显着降低。此外，氟康唑的副作用包括恶心、呕吐、腹痛、头痛、头晕、嗜睡、发烧、腹泻、皮疹和味觉改变。最严重的影响是肝毒性，但这通常会在治疗后停药后逆转。尽管如此，副作用的范围和严重程度可能会导致一些患者不遵守规定的药物治疗方案。克霉唑每天使用 4 至 5 次，持续 1 至 2 周。它的副作用包括味觉改变、恶心和胃部不适。再次强调，患者对处方药物治疗方案的依从性可能是一个问题，不仅因为副作用，还因为患者必须每天服用 4 至 5 剂。该项目的目标是开发一种安全有效、无副作用的漱口水来治疗头颈癌患者的口腔念珠菌病。具体目标包括实施当前的良好生产规范 (cGMP)，包括长期稳定性研究、向 FDA 提交研究性新药申请，以及在癌症患者中进行临床疗效试验以证明疗效。念珠菌属40-80%的正常人存在于口腔、肠道和阴道中。然而，念珠菌属。是极其机会主义的，如果免疫系统受到损害并且环境发生变化，念珠菌属。可能开始迅速繁殖，导致念珠菌病并产生潜在致命的疾病。鉴于全世界癌症患者数量众多，再加上其他高风险免疫功能低下的个体，例如感染艾滋病毒的患者，以及口干症（口干）患者数量的不断增加，安全有效且无副作用的漱口水可能会对公共健康产生深远的益处。