Extended Duration Varenicline for Smoking Among Cancer Patients: A Clinical Trial

描述（由申请人提供）：超过33-50%在诊断前吸烟的癌症患者在诊断和治疗后继续吸烟。癌症患者持续吸烟会减少生存时间、医疗效果和生活质量。迄今为止，对癌症患者戒烟干预的研究未能产生显著的治疗效果。因此，目前尚无基于证据的治疗模式来解决这一人群的烟草使用问题。随着癌症治疗的医学进步，癌症幸存者的人数越来越多——今天接近1200万——解决这一人群的尼古丁依赖问题是当务之急。最近的一次NCI会议呼吁对癌症患者尼古丁依赖的新治疗方法进行评估，以解决这一人群中明显的独特戒烟障碍，包括：高度的尼古丁依赖，高度的心理困扰和认知障碍，以及长期的复发时间。虽然公共卫生服务指南建议使用经批准的烟草使用药物进行急性治疗，但我们已经表明，延长治疗持续时间超过标准治疗持续时间可显著提高戒烟率，降低复发风险，并促进戒烟后的恢复。与标准疗程治疗相比，延长疗程治疗对高度尼古丁依赖和认知障碍的吸烟者特别有效，并增加了高度心理困扰的吸烟者的戒烟率。与其他治疗吸烟的药物相比，伐尼克兰可能对癌症患者特别有效，因为它对情绪和认知有有益的作用。因此，采用374例癌症患者的双盲安慰剂对照设计，我们将：1)比较标准伐尼克兰治疗（12周有效+ 12周安慰剂）与延长伐尼克兰治疗（24周有效）在增加第24周和第52周生物化学证实的7天点流行戒断程度上的差异~ 2)评估延长伐尼克兰治疗对生活质量的影响，包括伐尼克兰副作用~ 3)评估情感和认知障碍的变化作为延长伐尼克兰治疗对戒烟率影响的调节因子。我们还将探讨延长伐尼克兰治疗对戒烟率影响的潜在调节因子（例如，肿瘤部位和分期、诊断后的时间、治疗史、尼古丁依赖水平）。这项研究的意义在于解决了高吸烟率人群的问题，这一人群在尼古丁依赖治疗领域的研究不足，并且面临着独特的烟草相关不良健康影响的风险。本研究的创新之处在于，通过评估延长和标准持续时间的伐尼克兰治疗的疗效，可以更有效地解决这一人群中独特的戒烟障碍。这也是第一个使用伐尼克兰血药浓度作为依从性指标的研究。人们普遍认为，需要针对癌症患者尼古丁依赖的循证治疗方案。这项研究可能有助于指导实施这些计划的努力，并有助于确定延长治疗时间对更广泛的尼古丁依赖的益处。

DESCRIPTION (provided by applicant): Upwards of 33-50% of cancer patients who smoked prior to diagnosis continue to smoke following diagnosis and treatment. Continued smoking by cancer patients reduces survival time, medical treatment efficacy, and quality of life (QOL). To date, studies of smoking cessation interventions for cancer patients have failed to yield significant treatment effects. As such, currently, there is no evidence-based treatment model for addressing tobacco use in this population. With medical advances in cancer care yielding a growing constituency of cancer survivors - close to 12 million today - addressing nicotine dependence in this population is a priority. A recent NCI meeting called for the evaluation of novel treatments for nicotine dependence among cancer patients which address the unique barriers to cessation evident in this population, including: a high level of nicotine dependence, high levels of psychological distress and cognitive impairment, and a protracted relapse timeline. While PHS guidelines recommend acute treatment durations with approved medications for tobacco use, we have shown that extending the duration of treatment beyond the standard treatment duration significantly increases quit rates, reduces the risk for a relapse, and promotes recovery to abstinence following a lapse. Extended duration treatment is particularly efficacious for smokers with high levels of nicotine dependence and cognitive impairment, vs. standard duration treatment, and increases quit rates for smokers with high levels of psychological distress. Varenicline, vs. other medications for smoking, may be particularly effective for cancer patients given the drug's beneficial effects on affect ad cognition. Thus, using a double-blind placebo- controlled design with 374 cancer patients we will: 1) Compare standard varenicline treatment (12-weeks active + 12-weeks placebo) to extended varenicline treatment (24-weeks active) for increasing week 24 and week 52 biochemically-confirmed 7-day point prevalence abstinence~ 2) Assess the effects of extended varenicline therapy on QOL, including varenicline side effects~ and 3) Assess changes in affect and cognitive impairment as mediators of extended varenicline therapy's effect on quit rates. We will also explore potential moderators of the effect of extended varenicline treatment on quit rates (e.g., tumor site and stage, time since diagnosis, treatment history, level of nicotine dependence). This study is significant by addressing a population with high smoking rates, which has been under-studied in the area of nicotine dependence treatment, and is at risk for unique adverse tobacco-related health effects. This study is innovative by evaluating the efficacy of extended vs. standard duration varenicline treatment, which may more effectively address unique barriers to cessation in this population. This will also be the first study to use varenicline blood levels as a measure of adherence. There is widespread agreement that evidence-based treatment programs for nicotine dependence among cancer patients are needed. This study may help guide efforts to implement such programs and help determine the benefits of extended treatment duration for nicotine dependence more broadly. PUBLIC HEALTH RELEVANCE: About 33-50% of cancer patients who smoked before their diagnosis continue to smoke after their diagnosis and continued smoking reduces survival, quality of life, and the effectiveness of their medical treatment. To date, no study has demonstrated an efficacious approach to treating smoking among cancer patients perhaps because these treatments have not adequately addressed barriers to quitting smoking unique to this population, including a high level of nicotine dependence, a high level of psychological distress and cognitive impairment, and a protracted relapse time-line. We have found that extending treatment for nicotine dependence with the nicotine patch from the standard duration to 24-weeks increases quit rates, promotes recovery from a lapse, uniquely helps to mitigate the adverse effects of nicotine dependence and cognitive impairment on attempts to quit smoking, and increases quit rates for smokers with high levels of psychological distress. Varenicline, the most effective treatment currently available for nicotine dependence, reduces negative affect and promotes cognitive function. Thus, this clinical trial will compare standard duration (12- weeks) to extended duration (24-weeks) treatment with varenicline for nicotine dependence among cancer patients. The trial results may serve to guide the development of a treatment model for cancer patients and contribute to a growing literature demonstrating the enhanced efficacy of extended duration treatments for nicotine dependence.