EFFICACY OF TRICYCLICS IN TREATING CANCER PAIN

John T.法勒，大学神经病学助理教授 宾夕法尼亚州医学中心（UPMC）正在申请临床 研究者奖，以追求学术生涯的重点是临床 癌痛评估与管理研究 癌症是一个日益增长的死亡和残疾的原因， 美国每5例死亡中就有1例害怕痛苦和折磨 这是大多数癌症患者最关心的问题。尽管取得了进展， 疼痛管理，不到一半的人接受最佳和有效的治疗。 除了阿片类药物已被证明的有效性外， 设计研究，以判断如何最好地治疗这些疾病， 患者三环类抗抑郁药用于高达40%的癌症 患者虽然他们已经被证明可以显着减少非癌症 神经性疼痛，减少阿片类药物的使用量， 术后设置，他们还没有得到很好的研究癌症 患者确定其真正功效和决定因素， 预测可能受益的群体将对癌症产生重大影响 病人护理 Farrar博士长期以来一直对临床疼痛管理感兴趣， 癌症患者，建立了临床癌症疼痛管理 集团，并正在追求科学的UPMC硕士学位课程， 临床流行病学。他的兴趣包括预测建模和 药物流行病学应用于癌症疼痛的理解 评价和管理。该应用程序请求支持， 参加一个全面的职业发展计划，包括： 课程工作导致一个MS。临床流行病学：研究 Brian Strom博士的指导，临床中心主任 流行病学和生物统计学;与Russell博士进行广泛磋商 Portenoy，神经病学副教授兼镇痛药主任 纪念斯隆凯特琳癌症中心的疼痛服务;和一项研究 项目，这将有助于提供必要的知识和技能， 作为一名独立调查员追求成功的职业生涯。 该研究是一项双盲随机安慰剂对照试验 确定阿米替林辅助治疗的疗效 （平衡的非肾上腺素能和肾上腺素能）和地昔帕明（主要 去甲肾上腺素能）与活性安慰剂苯扎托品（以产生 类似的副作用谱），在癌症患者的疼痛， 通过阿片类药物治疗得到最佳控制治疗将从 12.5在10周内增加到150 mg，达到最大剂量或出现不可接受的副作用。 为了确定可能响应者的可能预测模型， 数据将作为队列研究进行重新分析。将采集血液样本 以评估镇痛是否与血液中的抗抑郁水平有关。的 这项研究的结果将对癌症的治疗产生重大影响。 疼痛通过证明或反驳这些常用的疗效， 药物，并提供具体的指导，为哪组患者 他们能从这种疗法中获益的地方

Dr. John T. Farrar, Assistant Professor of Neurology at the University of Pennsylvania Medical Center (UPMC) is applying for a Clinical Investigator Award to pursue an academic career focusing on the clinical investigation of cancer pain evaluation and management. Cancer is a growing cause of death and disability responsible for 1 out of every 5 deaths in the United States. Fear of pain and suffering are a major concern to most patients who develop cancer. Despite advances in pain management, less than half receive optimum and effective therapy. Beyond the proven effectiveness of opiates, there are very few well designed studies on which to base a judgment of how to best treat these patients. Tricyclic antidepressants are used in up to 40% of cancer patients. While they have been shown to significantly reduce noncancer neuropathic pain and reduce the amount of opiates used in the postoperative setting, they have not been well studied in cancer patients. Establishing their true efficacy and determining factors which predict the groups that may benefit would substantially influence cancer patient care. Dr. Farrar has a long-standing interest in clinical pain management in oncology patients, has established a Clinical Cancer Pain Management Group, and is pursuing the UPMC Master of Science Degree Program in Clinical Epidemiology. His interests include prognostic modeling and pharmacoepidemiology as applied to the understanding of cancer pain evaluation and management. The application requests support to allow him to undertake a comprehensive career development program including: formal course work leading to a M.S. in Clinical Epidemiology: a research preceptorship with Dr. Brian Strom, Director of the Center for Clinical Epidemiology and Biostatistics; extensive consultation with Dr. Russell Portenoy, Associate Professor of Neurology and Director of the Analgesic Pain Service at Memorial Sloan Kettering Cancer Center; and a research project, that will help provide the knowledge and skills necessary to pursue a successful career as an independent investigator. The proposed study is a double-blind randomized placebo-controlled trial to determine the efficacy of adjuvant therapy with amitriptyline (balanced nonadrenergic and serotonergic) and desipramine (primarily noradrenergic) against the active placebo benztropine (to produce a similar side effect spectrum), in cancer patients with pain that is not optimally controlled by opioid therapy. Therapy will be titrated from 12.5 to 150 mg in 10 weeks to maximum dose or unacceptable side effects. To determine a possible prediction model for the likely responders, the data will be re-analyzed as a cohort study. Blood samples will be drawn to evaluate if analgesia is related to anti-depressant blood levels. The results of this study will substantially impact on the care of cancer pain by either proving or disproving the efficacy of these commonly used drugs, and by providing specific guidance for which group of patients where they stand to benefit from this therapy.