Prevention of Depression in Head and Neck Cancer

 描述（由申请人提供）：抑郁症作为一种合并症，是实现积极结局、改善生活质量和提供高质量癌症和其他护理体验的障碍。头颈癌患者的新发抑郁症非常普遍，并导致许多负面的健康结果。氯胺酮已被证明对治疗抑郁症有快速的效果，包括我们自己对接受临终关怀的癌症患者的工作。这项创新探索性（R21）提案的目标是测试使用氯胺酮预防头颈癌患者抑郁症的可行性、安全性和耐受性。我们选择氯胺酮是因为它对头颈癌患者具有潜在的多重积极属性：已知的快速起效，在癌症疼痛中的有效性，多种给药途径，治疗抑郁症的能力，以及对共病焦虑的影响，所有这些都应该导致改善的结果，包括寿命和生活质量。考虑到头颈癌患者在治疗期间患抑郁症的比例很高，抑郁症对这些患者的结果产生了负面影响，以及以前在这一人群中进行的预防试验，头颈癌患者似乎是测试氯胺酮预防这些和其他癌症患者抑郁症的能力的良好逻辑首选。希望这项提案的结果将导致氯胺酮用于预防头颈部癌症患者抑郁症的最终试验（R 01提案），最终目标是预防抑郁症并改善这一人群以及其他癌症人群的健康状况。这一提议与国家癌症研究所对共病的研究重点一致，其中抑郁症可能是最具影响力的疾病之一。这也符合NIH改善健康结果的议程。具体目标1：可行性。研究在接受常规癌症护理和治疗的III期或IV期表皮样头颈癌患者中招募受试者参加口服氯胺酮与安慰剂的适应症预防试验的可行性。假设1：至少入组40例受试者，80%的随机化患者将完成试验。具体目标2：耐受性和安全性。在接受常规癌症护理和治疗的III期或IV期表皮样头颈癌患者中研究口服氯胺酮的安全性和耐受性。假设二：少于20%的随机接受口服氯胺酮的患者将因氯胺酮引起的不良或严重不良事件而脱落，这一比例与安慰剂组相当。探索性目标：本研究中收集的其他数据将用于探索氯胺酮对以下方面的影响：1）抑郁症的发生率，2）焦虑症状，3）疼痛水平和4）生活质量。未来的方向：这项研究将奠定 为一项更大规模的确定性试验（R 01提案）奠定基础，该试验用于预防头颈部和其他癌症患者的抑郁症。在未来，我们可能能够探索进一步的问题，可能是重要的预防和/或缓解抑郁症，痛苦，并提高生活质量的癌症患者。

 DESCRIPTION (provided by applicant): Depression as a co-morbidity is a barrier to achieving positive outcomes, improving quality of life, and delivering high-quality cancer and other care experiences. New onset depression in patients being treated for head and neck cancer is highly prevalent and leads to many negative health outcomes. Ketamine has been shown to have a rapid effect for treating depression, including in our own work in patients with cancer who were receiving hospice care. The goal of this innovative exploratory (R21) proposal is test the feasibility, safety, and tolerability of using ketamine for indicated prevention of depression in patients with head and neck cancer. We have chosen ketamine for its potential multiple positive attributes for patients with head/neck cancer: known rapid onset of action, proven efficacy in cancer pain, multiple routes of administration, ability to treat depression, and impact on co-morbid anxiety, all of which should lead to improved outcomes, including longevity and quality of life. Given the high proportion of patients with head and neck cancer who develop depression during treatment, the negative impacts that depression has on outcomes in these patients, and previous prevention trials in this population, head/neck cancer patients appear to be a good logical first choice to test ketamine's ability to prevent depression in these and other cancer patients. It is hoped that the outcomes of this proposal will lead to a definitive trial (R01 proposal) of ketamine for preventing depression in patients with head and neck cancer, with the ultimate goal of preventing depression and improving health outcomes in this, and possibly other, cancer populations. This proposal is consistent with the National Cancer Institute's research focus on co-morbidities, of which depression is likely one of the most impactful. It is also consistent with the NIH agenda of improving health outcomes. Specific Aim 1: Feasibility. To investigate the feasibility of enrolling subjects in a indicated prevention trial of oral ketamie vs placebo in patients receiving usual cancer care and treatment for stage III or IV epidermoid head/neck cancer. Hypothesis 1: At least 40 subjects will be enrolled and 80% of patients randomized will complete the trial. Specific Aim 2: Tolerability and Safety. To investigate the safety and tolerability of oral ketamine in patients receiving usual cancer care and treatment for stage III or IV epidermoid head/neck cancer. Hypothesis 2: Less than 20% of patients randomized to oral ketamine will drop-out due to adverse or serious adverse events attributed to ketamine, a proportion comparable to that in the placebo group. Exploratory Aims: Other data collected in this study will be used to explore ketamine's impact on: 1) incidence of depression, 2) anxiety symptoms, 3) pain levels, and 4) quality of life. Future Directions: This study will lay the groundwork for a larger, definitive trial (R01 proposal) of ketamine for the prevention of depression in patients with head and neck, and possibly other cancers. In the future, we may be able to explore further questions that may be of import for the prevention and/or relief of depression, suffering, and promotion of quality of life for cancer patients.