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

描述（由申请人提供）：在诊断前吸烟的癌症患者中，有33-50%的人在诊断和治疗后继续吸烟。癌症患者持续吸烟会降低生存时间、药物治疗效果和生活质量（QOL）。迄今为止，对癌症患者进行戒烟干预的研究未能产生显著的治疗效果。因此，目前还没有循证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是一个优先事项。最近的一次NCI会议呼吁评估癌症患者尼古丁依赖的新型治疗方法，这些方法可以解决这一人群中明显存在的独特戒烟障碍，包括：高水平的尼古丁依赖，高水平的心理困扰和认知障碍，以及长期复发的时间轴。 虽然PHS指南建议使用批准的烟草使用药物进行急性治疗，但我们已经证明，将治疗持续时间延长到标准治疗持续时间之外会显着增加戒烟率，降低复发风险，并促进戒烟后的恢复。 与标准持续时间治疗相比，延长持续时间治疗对具有高水平尼古丁依赖和认知障碍的吸烟者特别有效，并增加具有高水平心理困扰的吸烟者的戒烟率。伐尼克兰，与其他吸烟药物相比，可能对癌症患者特别有效，因为药物对影响和认知的有益作用。 因此，采用双盲安慰剂对照设计，纳入374例癌症患者，我们将：1）比较标准伐尼克兰治疗（12周活性药物+ 12周安慰剂）至延长伐尼克兰治疗（24周活性）增加第24周和第52周生物化学证实的7天点患病率戒断~ 2）评估延长伐尼克兰治疗对QOL的影响，包括伐尼克兰的副作用，以及3）评估作为延长伐尼克兰治疗对戒烟率影响的介质的情感和认知障碍的变化。我们还将探索延长伐尼克兰治疗对戒烟率影响的潜在调节因素（例如，肿瘤部位和阶段、自诊断以来的时间、治疗史、尼古丁依赖水平）。这项研究的意义在于解决了吸烟率高的人群，这在尼古丁依赖治疗领域研究不足，并且存在独特的烟草相关不良健康影响的风险。这项研究是创新的，通过评估延长与标准持续时间伐尼克兰治疗的疗效，这可能更有效地解决这一人群中独特的戒烟障碍。这也将是第一个使用伐尼克兰血液水平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计划。这项研究可能有助于指导实施这些计划的努力，并有助于更广泛地确定延长尼古丁依赖治疗时间的益处。

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.