Palliating EGFR Inhibitor Rash in African American and Other Cancer Patients

摘要 表皮生长因子受体(EGFR)抑制剂包括常用的处方药 一类可提高多种恶性肿瘤患者存活率的药物。皮疹， 尤其是在面部，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选择，以及 有时需要停止癌症治疗。我们已经发表了定性研究 从出现这种皮疹的患者那里得知它会导致皮肤疼痛， 心理困扰和社会孤立。一位病人说：“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？’我对此感到难为情 另一位网友评论说，我只是告诉他们，给我打电话会更好， 别来探望我。“另一位网友描述说，“我能感觉到全身发痒和灼热。”一些人 调查人员表示，非裔美国人患者不会遭受这些痛苦。 症状。在这里，我们假设他们有，他们有色素的皮肤可能 伪装皮疹，但这种皮疹仍然会给他们带来身体和心理上的痛苦。 基于我们的数据(一项933名患者的流行病学研究表明，皮疹在 男性；显示局部抗雄激素有效的试点临床试验数据；以及 EGFR抑制剂患者皮肤活检中雄激素依赖性基因图谱的研究 皮疹)和来自其他细胞的数据(一些黑素细胞过度表达雄激素和 雄激素受体)，我们假设皮疹是由雄激素驱动的，局部用药 抗雄激素酮康唑在所有患者中都能缓解，包括非裔美国人。 癌症患者。在目标1中，我们将采访那些患有 开发了这种皮疹，并将使用新的定性方法来探讨他们的 假想的心理和皮肤痛苦。在目标2中，我们将进行 含酮康唑的随机、双盲、安慰剂对照试验(一种外用抗癌药物 雄激素)，以确定该药物是否缓解了种族差异队列中的皮疹 并探索它是否通过调节雄激素依赖基因来实现这一点，正如所暗示的那样 敬更高的。这项调查的长期目标是减少痛苦和 改善包括非洲裔美国人在内的所有患者的生活质量 患有EGFR抑制剂引起的皮疹。

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.