Treatment of Refractory Nausea

摘要 尽管根据美国临床肿瘤学会发表的 （ASCO）指南，化疗相关恶心仍然是一个临床显著问题， 病人的问题比化疗引起的呕吐更严重。治疗后恶心是 发生的可能性是呕吐的三倍本研究的主要目的1是检查是否控制 在首次化疗后发生化疗诱导的恶心和呕吐（CINV）的患者中， 化疗，尽管接受适当的ASCO推荐的止吐药，可以改善 在第1-4天添加丙氯拉嗪（Compazine®）或奥氮平（Zyprexa®）。当前ASCO 难治性CINV指南建议肿瘤学家考虑加用奥氮平（Zyprexa®）或多巴胺 止吐方案的拮抗剂，如丙氯拉嗪（Compazine®），但这些只是许多中的两个 控制难治性CINV的可能策略，其中没有一个经过经验检验。主要目标2 奥氮平是一种比普鲁氯拉嗪更新、更昂贵的止吐药， 当与阿瑞匹坦联合使用时， 帕洛诺司琼和地塞米松。本研究随访了我们最近的五个多中心CINV 问题研究 我们还将讨论一个额外的问题，控制化疗相关的恶心。即 缺乏基于药理学的模型预测化疗引起的恶心， 高度致吐化学治疗剂不仅考虑到接受最新技术， 止吐方案以及患者因素如年龄、种族、民族、饮酒量、期望值， 焦虑、治疗前早晨的恶心程度和恶心既往史。这一预测 模型将是止吐指南的重要补充。 拟定研究包括两个部分，第1周期进行筛选和一些评估， 研究的随机化部分（N = 334）发生在第2周期。在第1周期，我们将同意化疗 初治乳腺癌患者即将开始四种特定化疗方案之一， 潜在致吐性，并计划接受符合ASCO临床实践的止吐方案 指南我们预计需要在第1周期同意约800例患者，以达到我们的第2周期目标 number.周期2部分将在发生中度或重度恶心的患者中进行 在第1周期。这是一项III期、随机、双盲、安慰剂对照、2组研究（N = 334）， 建立在我们之前的CINV研究基础上，并研究了经历过CINV的患者的CINV最佳控制 初始化疗后的CINV。本研究将由罗切斯特癌症大学实施 中心（URCC）NCI社区肿瘤研究计划（NCORP）研究基地，我们的办公室管理。

Abstract Despite the provision of antiemetic agents in accordance with published American Society of Clinical Oncology (ASCO) guidelines, chemotherapy-related nausea remains a clinically significant issue that is rated by patients as a greater problem than chemotherapy-related vomiting. Nausea following treatment is three times more likely to occur than vomiting. Primary Aim 1 of this study examines whether control of nausea in patients who experienced chemotherapy-induced nausea and vomiting (CINV) following their initial chemotherapy despite receiving the appropriate ASCO-recommended antiemetics can be improved by the addition of either prochlorperazine (Compazine®) or olanzapine (Zyprexa®) on days 1-4. Current ASCO guidelines for refractory CINV suggest that oncologists consider adding olanzapine (Zyprexa®) or a dopamine antagonist such as prochlorperazine (Compazine®) to the antiemetic regimen, but these are only two of many possible strategies for control of refractory CINV, none of which has been empirically tested. Primary Aim 2 will test whether olanzapine, which is a newer, more expensive antiemetic drug than prochlorperazine, is more effective than prochlorperazine in controlling nausea when used in combination with aprepitant, palonosetron and dexamethasone. This study follows up on the most recent of our five multicenter CINV studies. We will also address an additional problem regarding control of chemotherapy-related nausea. That is the lack of empirically-based models predicting chemotherapy-induced nausea from common moderately or highly emetogenic chemotherapeutic agents that take into account not only receipt of a state-of-the-art antiemetic regimen but also patient factors such as age, race, ethnicity, alcohol consumption, expectancy, anxiety, degree of nausea on the morning prior to treatment, and prior history of nausea. This prediction model will be an important addition to the antiemetic guidelines. The proposed study consists of two parts with screening and some assessments occurring at Cycle 1 and the randomized portion of the study (N = 334) occurring at Cycle 2. At Cycle 1, we will consent chemotherapy naïve breast cancer patients about to begin one of four specified chemotherapy regimens with high/moderate emetogenic potential and scheduled to receive an antiemetic regimen that conforms to ASCO Clinical Practice Guidelines. We anticipate needing to consent approximately 800 patients at Cycle 1 to meet our Cycle 2 target number. The Cycle 2 portion will be conducted in those patients who experienced moderate or greater nausea at Cycle 1. It will be a Phase III randomized, double-blinded, placebo-controlled, 2-arm study (N = 334) that builds upon our prior CINV studies and investigates optimal control of CINV in patients who experienced CINV following initial chemotherapy. This study will be implemented by the University of Rochester Cancer Center (URCC) NCI Community Oncology Research Program (NCORP) Research Base that our office manages.