Palliating EGFR Inhibitor Rash in African American and Other Cancer Patients

摘要 表皮生长因子受体（EGFR）抑制剂包括通常规定的 这类药物可以提高各种恶性肿瘤患者的生存率。皮疹， 特别是面部，是最常见的不良事件，发生在50-90%的 10-20%的患者病情严重，缺乏有效的姑息治疗方案， 有时需要停止癌症治疗我们发表了定性研究 从患上这种皮疹的病人那里得知它会导致皮肤疼痛， 心理压力和社会孤立一位病人说：“我的脸看起来很糟糕。 如果我去见我的朋友，他们会说，‘你怎么了。“我很自觉 了另一位评论说：“我只是告诉他们，他们最好给我打电话， 别来看我”另一个人描述说：“我能感觉到全身发痒和灼烧。“一些 研究人员认为，非洲裔美国人的患者并不患有这些疾病， 症状在这里，我们假设他们有，他们的有色皮肤可能 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933例患者的流行病学研究，显示皮疹在 男性;显示局部抗雄激素获益的初步临床试验数据;以及 来自EGFR抑制剂患者皮肤活检的雄激素依赖性基因谱 皮疹）和其他数据（一些黑素细胞过度表达雄激素， 雄激素受体），我们假设这种皮疹是雄激素驱动的， 抗雄激素药物酮康唑可缓解所有患者，包括非裔美国人 癌症患者。在目标#1中，我们将采访非洲裔美国患者， 开发了这种皮疹，并将使用新的定性方法来探讨他们的 假设的心理和皮肤痛苦。在目标#2中，我们将进行 一项随机、双盲、安慰剂对照试验，使用酮康唑（一种局部抗 雄激素），以确定该药物是否能缓解种族多样性队列中的皮疹 并探索它是否通过调节雄激素依赖基因来实现这一点， 到上面。这条调查路线的长期目标是减少痛苦， 改善所有患者的生活质量-包括非洲裔美国患者- 患有EGFR受体诱导的皮疹。

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.