Palliating EGFR Inhibitor Rash in African American and Other Cancer Patients

缓解非裔美国人和其他癌症患者的 EGFR 抑制剂皮疹

• 批准号: 9274475
• 负责人: Aminah Jatoi
• 金额: $ 38.53万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9274475
• 关键词: Adverse effects; Adverse event; African American; Androgen Antagonists; Androgen Receptor; Androgens; Antineoplastic Agents; Biopsy; Cancer Patient; Cetuximab; Clinical Data; Clinical Trials; Colorectal Cancer; Conscious; Cutaneous; Data; Development; Distress; Double-Blind Method; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Exanthema; Face; Feasibility Studies; Friends; Genes; Goals; Head and Neck Cancer; Hormones; Hospitalization; Interview; Investigation; Ketoconazole; Lead; Learning; Life; Limb structure; Malignant Neoplasms; Malignant neoplasm of lung; Mediating; Messenger RNA; Methodology; Morbidity - disease rate; National Comprehensive Cancer Network; Pain; Patients; Pharmaceutical Preparations; Pigments; Pruritus; Published Comment; Publishing; Qualitative Methods; Qualitative Research; Quality of life; Race; Randomized; Reporting; Research Personnel; Risk; Skin; Social isolation; Symptoms; Testing; Time; United States Food and Drug Administration; Visit; androgen sensitive; cancer therapy; cohort; double-blind placebo controlled trial; emotional distress; epidemiology study; ethnic difference; experience; high risk; improved; male; melanocyte; men; novel; novel therapeutics; overexpression; palliate; palliative; patient oriented; psychologic; psychological distress; psychosocial; racial diversity; randomized placebo controlled trial; social

ABSTRACT Epidermal growth factor receptor (EGFR) inhibitors comprise a commonly prescribed class of drug that improves survival in patients with a variety of malignancies. Rash, particularly on the face, is the most common adverse event and occurs in 50-90% of patients, is severe in 10-20% of patients, lacks effective palliative options, and sometimes requires stopping cancer therapy. We have published qualitative research from patients who developed this rash and learned that it leads to cutaneous pain, psychological distress, and social isolation. One patient stated, "My face looks so bad that if I go see my friends, they say, 'What happened to you.' I am self-conscious about that." Another commented, “I just told them they would be better off just calling me, don't come visit.” Another described, "I can feel the itch and burn all over." Some investigators have suggested that African American patients do not suffer these symptoms. Here, we hypothesize that they do, that their pigmented skin might camoflage the rash, but that this rash still causes them physical and psychological pain. Building on our data (a 933-patient epidemiologic study that shows rash is worse in men; pilot clinical trial data that show benefit with a topical anti-androgen; and an androgen-dependent gene profile from skin biopsies from patients with EGFR inhibitor rash) and on data from others (some melanocytes overexpress androgens and androgen receptors), we hypothesize this rash is androgen-driven and that the topical antiandrogen, ketoconazole, palliates it in all patients, including African American cancer patients. In Aim #1, we will interview African American patients who have developed this rash and will use novel qualitative methods to probe into their hypothesized psychological and cutaneous distress. In Aim #2, we will conduct a randomized, double-blinded, placebo-controlled trial with ketoconazole (a topical anti- androgen) to determine whether this agent palliates rash within a racially diverse cohort and to explore whether it does so by modulating androgen-dependent genes, as alluded to above. The long-term goal of this line of investigation is to reduce suffering and improve the quality of life of all patients -- including African American patients -- who suffer from EGFR inhibitor-induced rash.

抽象的 表皮生长因子受体 (EGFR) 抑制剂包括常用的处方药 一类可提高多种恶性肿瘤患者生存率的药物。 尤其是面部，是最常见的不良事件，发生在 50-90% 的人中 10-20% 的患者病情严重，缺乏有效的姑息治疗方案，并且 有时需要停止癌症治疗。我们已经发表了定性研究。 从出现这种皮疹并得知它会导致皮肤疼痛的患者那里， 一名患者表示，“我的脸看起来很糟糕。 如果我去看我的朋友，他们会说，“你怎么了？” 那个。”另一个评论道，“我只是告诉他们，他们最好给我打电话， 别来拜访。”另一个人描述道，“我能感觉到全身发痒和灼痛。” 研究人员表示，非洲裔美国患者不会遭受这些痛苦 在这里，我们研究了他们的色素皮肤可能会出现的症状。 掩盖皮疹，但这种皮疹仍然会给他们带来身体和心理上的痛苦。 根据我们的数据（一项针对 933 名患者的流行病学研究表明，皮疹在 男性；试点临床试验数据显示局部抗雄激素药物的益处； 来自 EGFR 抑制剂患者皮肤活检的雄激素依赖性基因谱 皮疹）以及其他人的数据（一些黑素细胞过度表达雄激素和 雄激素受体），我们认为这种皮疹是雄激素驱动的，并且局部用药 抗雄激素酮康唑可以缓解所有患者的症状，包括非裔美国人 在目标#1中，我们将采访患有癌症的非裔美国患者。 出现了这种皮疹，并将使用新颖的定性方法来探讨其 在目标#2中，我们将进行 酮康唑（一种局部抗- 雄激素）以确定该药物是否在种族多样化的群体中起到缓解作用 并探索它是否通过调节雄激素依赖性基因来实现这一点，正如所提到的 上述调查的长期目标是减少痛苦和减少痛苦。 改善所有患者（包括非裔美国患者）的生活质量 患有 EGFR 抑制剂引起的皮疹。