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: 7289861
• 负责人: BAKUL M BHATT
• 金额: $ 35.67万
• 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 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7289861
• 关键词: Abdominal Pain; Acute; Adverse effects; Aftercare; Animals; Antifungal Agents; Antifungal Therapy; Bacteria; Biocide; Biological Assay; Blood; Cancer Patient; Candida; Candida albicans; Candidiasis; Cells; Cheek structure; Clinical; Clinical Trials; Communities; Coupled; Daily; Dental Calculus; Dental Enamel; Dentists; Development; Diarrhea; Disease; Dizziness; Doctor of Medicine; Doctor of Pharmacy; Doctor of Philosophy; Dose; Drowsiness; Drug Formulations; Drug Prescriptions; End Point; Endocrinologist; Environment; Esophageal; Exanthema; Fever; Fluconazole; Food; Fungal Drug Resistance; Fungemia; Goals; Guanosine Monophosphate; HIV; Hamsters; Head and Neck Cancer; Headache; Health Benefit; Hepatotoxicity; Human; Hypersensitivity; Immune system; In Vitro; Individual; Infection; Intestines; Investigational Drugs; Investigational New Drug Application; Iodine; Life; Malignant Neoplasms; Metabolic; Miconazole; Microbial Biofilms; Molecular; Mouthwash; Mycoses; Nausea; Nausea and Vomiting; Numbers; Oral; Oral candidiasis; Oral cavity; Oral mucous membrane structure; Organism; Oropharyngeal; Participant; Patients; Periodontitis; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Predisposition; Principal Investigator; Public Health; Radiation Oncologist; Radiation therapy; Rattus; Research; Research Personnel; Resistance; Risk; Safety; Severities; Site; Stomach; System; Tablets; Taste Perception; Time; Tooth Erosion; Toxic effect; Treatment Effectiveness; Treatment Protocols; United States Food and Drug Administration; Vagina; Virus; Week; Xerostomia; Yeasts; antimicrobial; candidemia; chemotherapy; clinical efficacy; compliance behavior; cytotoxic; day; design; dosage; efficacy trial; experience; fungus; head and neck cancer patient; immunosuppressed; in vitro Assay; in vitro Model; killings; microbicide; novel; thrush (bird)

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(申请人提供)：口腔念珠菌病(口咽部念珠菌病或鹅口疮)是一种常见的感染在免疫抑制的个人，如果不钝化，可过渡到食道念珠菌病或危及生命的念珠菌症。这些潜在威胁生命的真菌感染源于个体的内源性菌群。对于癌症患者，放射治疗或化疗会进一步抑制免疫系统，导致患者更容易患上口腔念珠菌病和/或系统性真菌感染(真菌血症，一种通过血液传播的真菌感染)。口腔念珠菌病一般用全身抗真菌药物或口腔漱口水来治疗。氟康唑片和克霉唑片是最受欢迎的治疗方法。氟康唑被指定用于治疗口腔念珠菌病，每日单剂，持续两周。然而，生物膜中的某些念珠菌对包括氟康唑在内的抗真菌药物的敏感性显著降低。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。最严重的影响是肝脏毒性，但当药物停用后，这种毒性通常会在治疗后逆转。尽管如此，副作用的范围和严重性可能会导致一些患者不遵守他们的处方药物方案。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。同样，患者对处方药物方案的依从性可能会成为一个问题，不仅因为副作用，还因为患者必须每天服用4至5剂。本项目的目标是开发一种安全、有效、无副作用的含漱液来治疗头颈部癌症患者的口腔念珠菌病。具体目标包括实施目前的良好制造规范(CGMP)，包括长期稳定性研究，向FDA提交调查性新药申请，以及在癌症患者中进行临床疗效试验以证明疗效。假丝酵母菌存在于40-80%的正常人的口腔、肠道和阴道中。然而，假丝酵母(Candida spp.)都是极端机会主义的，如果免疫系统受到损害，环境发生变化，念珠菌就会出现。可以开始快速繁殖，导致念珠菌病并产生一种潜在的致命疾病。鉴于全世界有大量癌症患者，再加上其他高风险免疫受损患者，如艾滋病毒感染者，以及越来越多的口干症(口干)患者，安全、有效、无副作用的漱口水可能会对公众健康产生深远的好处。