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

项目总结

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.