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

描述(申请人提供)：在确诊前吸烟的癌症患者中，超过33%-50%的患者在确诊和治疗后继续吸烟。癌症患者持续吸烟会降低患者的生存时间、医疗效果和生活质量。到目前为止，针对癌症患者的戒烟干预研究尚未产生显著的治疗效果。因此，目前还没有解决这一人群烟草使用问题的循证治疗模式。随着癌症治疗方面的医学进步产生了越来越多的癌症幸存者--目前接近1200万人--解决这一人群中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疗法进行评估，这些疗法解决了在这一人群中明显存在的戒烟独特障碍，包括：高度的尼古丁依赖、高度的心理痛苦和认知障碍，以及长期的复发时间表。虽然PHS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，将治疗持续时间延长到标准治疗持续时间之外，显著增加戒烟率，降低复发风险，并促进在失误后恢复戒烟。与标准持续时间治疗相比，延长持续时间治疗对尼古丁依赖程度高和认知障碍程度高的吸烟者特别有效，并增加了心理困扰程度高的吸烟者的戒烟率。与其他治疗吸烟的药物相比，varenicline可能对癌症患者特别有效，因为这种药物对情感和认知有好处。因此，我们将对374名癌症患者采用双盲安慰剂对照设计：1)比较标准varenicline治疗(12周有效+12周安慰剂)和延长varenicline治疗(24周有效)在增加第24周和52周生化确认的7天点戒断率方面的作用~2)评估延长varenicline治疗对生活质量的影响，包括varenicline副作用~3)评估作为延长varenicline治疗对戒断率影响的中介因素的情感和认知障碍的变化。我们还将探索延长varenicline治疗对戒烟率影响的潜在调节因素(例如，肿瘤部位和分期、自诊断以来的时间、治疗史、尼古丁依赖程度)。这项研究对解决吸烟率高的人群具有重要意义，这一人群在尼古丁依赖治疗领域一直未得到充分研究，并面临与烟草有关的独特不利健康影响的风险。这项研究是创新的，它评估了延长疗程的varenicline治疗与标准持续时间治疗的疗效，它可能更有效地解决这一人群中独特的戒烟障碍。这也将是第一项使用varenicline血液水平作为依从性衡量标准的研究。人们普遍认为，癌症患者中尼古丁依赖的循证治疗计划是必要的。这项研究可能有助于指导实施此类计划的努力，并有助于更广泛地确定延长尼古丁依赖治疗期限的好处。

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.