Atorvastatin to Reduce Cisplatin-Induced Hearing Loss in Head and Neck Cancer Patients

项目总结 顺铂是一种广泛使用的有效药物，用于治疗各种癌症。顺铂有几个 严重的副作用，包括永久性听力丧失(耳毒性)，降低癌症的生活质量 幸存者，并可以限制剂量。在不影响顺铂的治疗效果的情况下，有一种主要的临床需求尚未得到满足，即减少顺铂引起的听力损失。我们出版的关于动物的研究成果 模型表明，他汀类药物是FDA批准的一类药物，通常用于管理 高胆固醇血症，降低顺铂引起的听力损失。对正在接受治疗的人类的回顾数据 顺铂治疗头颈部鳞状细胞癌(HNSCC)表明，受试者服用 与不服用任何他汀类药物的患者相比，阿托伐他汀显著减少了顺铂所致的听力损失 毒品。这项研究是一项多点、随机、安慰剂对照的干预试验，旨在确定 阿托伐他汀在多大程度上减少头颈癌患者顺铂引起的听力损失。AS 主要目的：我们将确定阿托伐他汀在多大程度上降低高血压的发生率和严重程度。 顺铂致HNSCC患者听力损失的研究患有未经治疗的HNSCC的受试者 计划接受以顺铂为基础的放化疗(CRT)且尚未服用他汀类药物的患者将 在CRT期间，每天随机接受口服阿托伐他汀(40 Mg)或安慰剂。基线测听 阈值将在顺铂治疗开始前和完成所有周期后3个月再次测量。 顺铂。主要结果是以下CTCAEv5.0 2级听力损失的发生率的差异 基于顺铂的CRT比较服用阿托伐他汀和服用安慰剂的受试者。作为次要角色 目的：我们将评估阿托伐他汀组和安慰剂组在患者报告结果方面的差异。 关注整体生活质量、听力、平衡、耳鸣和周围神经病。作为一个探索者 目的：我们将评估他汀类药物是否影响HNSCC患者的生存。受试者将被跟踪 CRT后两年评估两年的总体和无病生存期。

PROJECT SUMMARY Cisplatin is a widely-used and effective drug that is used to treat a variety of cancers. Cisplatin has several significant side effects, including permanent hearing loss (ototoxicity), which reduces quality of life for cancer survivors and can be dose limiting. There is a major unmet clinical need for therapies that reduce cisplatin-induced hearing loss without compromising the therapeutic efficacy of cisplatin. Our published work in animal models suggests that statins, a class of FDA-approved drugs that are commonly used to manage hypercholesterolemia, reduce cisplatin-induced hearing loss. Retrospective data in humans undergoing cisplatin therapy to treat head and neck squamous cell carcinoma (HNSCC) indicate that subjects taking atorvastatin had significantly reduced cisplatin-induced hearing loss compared to those not taking any statin drug. This study is a multi-site, randomized, placebo-controlled interventional trial designed to determine the extent to which atorvastatin reduces cisplatin-induced hearing loss in patients with head and neck cancer. As primary objective, we will determine the extent to which atorvastatin reduces the incidence and severity of cisplatin-induced hearing loss in patients with HNSCC. Subjects with previously untreated HNSCC who are scheduled for cisplatin-based chemoradiation therapy (CRT) and are not already taking a statin will be randomized to receive either oral atorvastatin (40 mg) or placebo daily throughout CRT. Baseline audiometric thresholds will be measured prior to onset of cisplatin therapy and again 3 months after completion of all cycles of cisplatin. The primary outcome is the difference in incidence of a CTCAEv5.0 Grade 2 hearing loss following cisplatin-based CRT comparing subjects taking atorvastatin vs. those taking a placebo. As a secondary objective, we will assess for differences between atorvastatin and placebo groups in patient-reported outcomes focusing on overall quality of life, hearing, balance, tinnitus, and peripheral neuropathy. As an exploratory objective, we will estimate whether statins affect survival in patients with HNSCC. Subjects will be followed for two years after CRT to estimate 2-year overall and disease-free survival.