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（由申请人提供）：口服念珠菌病（口咽念珠菌或鹅口疮）是免疫抑制个体中常见的感染，如果不钝化，可以转移到食管食道念珠菌或危及生命的念珠菌。这些潜在的威胁生命的真菌感染起源于个人的内源性菌群。对于癌症患者，放射治疗或化学疗法进一步抑制了免疫系统，并使患者变得更容易受到口腔念珠菌病和/或全身真菌感染（真菌，一种由血液传播的真菌感染）。口服念珠菌病通常用全身性抗真菌剂或口服冲洗治疗。氟康唑片剂和氯咪唑杆杆是最受欢迎的疗法。氟康唑被指示用于治疗口服念珠菌病，每日剂量两周。但是，生物膜中的某些念珠菌生物对包括氟康唑在内的抗真菌药物的敏感性大大降低。此外，氟康唑的副作用包括恶心，呕吐，腹部疼痛，头痛，头晕，嗜睡，发烧，腹泻，皮疹，味觉变化。最严重的作用是肝脏毒性，但这通常在停止药物后治疗后逆转。但是，副作用的范围和严重程度可能导致某些患者不符合其处方药方案。每天使用4至5次，持续1至2周。它的副作用包括改变口味，恶心和胃部不适。再次，患者遵守规定的药物方案不仅是一个问题，这不仅是因为副作用，而且还因为患者每天必须服用4至5剂。该项目的目的是开发安全有效的漱口水，而没有副作用来治疗头颈癌患者的口腔念珠菌病。具体目的包括实施当前的良好制造实践（CGMP），包括长期稳定性研究，向FDA提交研究新药应用，以及在癌症患者中进行临床疗效试验以证明功效。念珠菌属。存在于40-80％的正常个体，肠道和阴道中。但是，念珠菌属。是极端机会主义的，如果免疫系统受到损害，环境会发生变化，念珠菌属。可以开始迅速繁殖，导致念珠菌病并导致潜在的致命疾病。鉴于全世界大量的癌症患者，再加上其他高风险免疫受损的人，例如感染了艾滋病毒的患者，以及越来越多的静脉病患者（干嘴）患者数量越来越多，没有副作用的安全有效的口腔冲洗可能会带来深远的公共健康益处。