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

延长伐尼克兰治疗癌症患者的吸烟时间：一项临床试验

• 批准号: 8372446
• 负责人: Robert A Schnoll
• 金额: $ 64.82万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8372446
• 关键词: Abstinence; Acute; Address; Adherence; Adverse effects; Affect; Agreement; Area; Behavior Therapy; Blood; Bupropion; Cancer Center; Cancer Patient; Cancer Survivor; Clinical Trials; Cognition; Comprehensive Cancer Center; Data; Development; Diagnosis; Double-Blind Method; Effectiveness; Evaluation; Evidence based treatment; Exhibits; General Population; Guidelines; Health; Impaired cognition; Intervention; Literature; Measures; Mediating; Mediator of activation protein; Medical; Mental Depression; Modeling; Nicotine Dependence; Nurses; Patients; Pharmaceutical Preparations; Pharmacotherapy; Physicians; Placebo Control; Placebos; Population; Prevalence; Primary Neoplasm; Process; Quality of life; Recording of previous events; Recovery; Recruitment Activity; Relapse; Research; Risk; Second Primary Cancers; Site; Smoke; Smoker; Smoking; Smoking Cessation Intervention; Staging; Testing; Time; TimeLine; Tobacco; Tobacco use; Treatment Efficacy; United States National Institutes of Health; United States Public Health Service; Withholding Treatment; base; cancer care; cancer diagnosis; cognitive function; design; effective therapy; experience; improved; innovation; meetings; nicotine patch; novel; placebo controlled study; programs; psychological distress; smoking cessation; standard care; treatment duration; treatment effect; treatment program; tumor; varenicline

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.

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。 公共卫生相关性：在确诊前吸烟的癌症患者中，约有33%-50%在确诊后继续吸烟，继续吸烟会降低患者的生存率、生活质量和医疗效果。到目前为止，还没有研究证明治疗癌症患者吸烟的有效方法，可能是因为这些治疗方法没有充分解决这一人群特有的戒烟障碍，包括高度尼古丁依赖、高度心理困扰和认知障碍，以及长期复发的时间线。我们发现，将尼古丁贴片的尼古丁依赖治疗从标准持续时间延长到24周，可以提高戒烟率，促进戒烟恢复，特别有助于减轻尼古丁依赖和认知障碍对戒烟尝试的不利影响，并提高有高度心理困扰的吸烟者的戒烟率。Varenicline，目前最有效的治疗方法 尼古丁依赖，减少负面情绪，促进认知功能。因此，这项临床试验将比较癌症患者中使用varenicline的标准疗程(12周)和延长疗程(24周)对尼古丁依赖性的影响。试验结果可能有助于指导癌症患者治疗模式的发展，并有助于越来越多的文献证明延长疗程治疗尼古丁依赖的疗效增强。