Chemotherapy and Disability in Older Hormone-Refractory Prostate Cancer Patients

简介(申请人提供)：前列腺癌是65岁及以上男性最常见的癌症类型，也是癌症相关死亡的第二大原因。与最好的姑息治疗相比，新开发的化疗药物和方案提高了前列腺癌患者的存活率、应答率和姑息治疗，这些患者达到了激素抵抗阶段。然而，化疗带来的治疗益处伴随着不良事件，导致老年癌症患者的功能受限和残疾。此外，与衰老相关的病理生理脆弱性和潜在的社会脆弱性使老年激素难治性前列腺癌(HRPC)患者损害宿主，并使他们在化疗期间面临更高的负面功能状态结果的风险。考虑到残疾对治疗依从性、制度化和死亡的影响，需要有效的干预措施来纠正这一规模庞大且受到损害的患者群体在化疗期间的残疾发展。为了制定这样的干预措施，需要从经验上解决化疗期间残疾发展模式和危险因素方面的知识差距。这项拟议的研究扩展了先前的研究，前瞻性地检查了老年HRPC患者化疗期间功能限制和残疾的变化，以及一系列生物和社会风险因素对残疾发展的影响。这项研究的具体目的是：(1)描述老年HRPC患者在前6个化疗周期中功能受限和残疾的变化，以及功能受限和残疾之间的纵向关系；(2)测试生物和社会危险因素对老年HRPC患者在前6个化疗周期中残疾发展的影响。据推测，与化疗开始前相比，在化疗的前6个周期中，功能受限和残疾水平将会增加。进一步假设功能受限和残疾的变化率将是正相关的。最后，假设随着时间的推移，诸如虚弱的存在、更多的合并症、较低的社会经济地位和不充分的社会支持等风险因素将与残疾的更大增加相关。为了实现这些目标，将在前6个化疗周期之前和期间前瞻性地收集关于功能限制和残疾的自我报告数据，并在化疗开始之前收集关于生物和社会风险因素的自我报告和基于绩效的信息。这项拟议的研究将有助于更好地了解老年HRPC患者化疗期间残疾发展的短期模式和风险因素；将为未来研究老年HRPC患者残疾的长期轨迹奠定基础；并有望为制定干预措施以避免接受化疗的老年HRPC患者的残疾发展提供信息。这项研究的发现可能有助于实现2010年健康人目标，即减少癌症导致的疾病、残疾和死亡。 公共卫生相关性：更好地了解老年激素抵抗前列腺癌患者化疗期间功能受限和残疾的短期变化，以及风险因素对残疾发展的影响，可能有助于制定更有效的干预措施，以防止或减少残疾发展，从而改善公共健康。这项拟议的研究将检查功能限制和残疾的变化，以及随着时间的推移生物和社会风险因素与残疾变化之间的关系。

DESCRIPTION (provided by applicant): Abstract: Prostate cancer is the most frequent type of cancer and second cause of cancer-related death in men aged 65 and older. Compared to best palliative care, newly developed chemotherapy drugs and regimens increased survival, response rate, and palliation in prostate cancer patients who reached the hormone refractory stage of the disease. Therapeutical benefits from chemotherapy, however, are accompanied by adverse events shown to result in functional limitations and disability in older cancer patients. Additionally, aging-related pathophysiological vulnerability and potential social vulnerability make older hormone-refractory prostate cancer (HRPC) patients compromised hosts and place them at increased risk for negative functional status outcomes during chemotherapy. Given the impact of disability on treatment compliance, institutionalization, and death, effective interventions are needed to amend the development of disability during chemotherapy in this sizeable and compromised patient group. To develop such interventions, knowledge gaps in patterns of and risk factors for disability development during chemotherapy need to be empirically addressed. This proposed study extends previous research by prospectively examining changes in functional limitations and disability, and the impact of a series of biologic and social risk factors on disability development during chemotherapy in older HRPC patients. The specific aims of this proposed study are: (1) to describe changes in functional limitations and disability, and the longitudinal relationship between functional limitations and disability in older HRPC patients during the first 6 cycles of chemotherapy; and (2) to test the influences of biologic and social risk factors on the development of disability in older HRPC patients during the first 6 cycles of chemotherapy. It is hypothesized that levels of functional limitations and disability will increase during the first 6 cycles of chemotherapy compared to prior to chemotherapy initiation. It is further assumed that the rates of change for functional limitations and disability will be positively correlated. Finally, it is hypothesized that risk factors such as presence of frailty, more comorbidity, lower socioeconomic status, and inadequate social support will be associated with greater increases in disability over time. To accomplish these aims, self- reported data on functional limitations and disability will be collected prospectively prior and during the first 6 chemotherapy cycles, and self-reported and performance-based information on biologic and social risk factors will be collected before chemotherapy initiation. The proposed study will contribute to a better understanding of short-term patterns of and risk factors for disability development during chemotherapy in older HRPC patients; will lay the foundation for a future study examining long-term trajectories of disability in older HRPC patients; and is expected to inform the development of an intervention to avoid disability development in older HRPC patients receiving chemotherapy. The findings from this study may contribute to the achievement of the Healthy People 2010 goal of reducing illness, disability, and death caused by cancer. PUBLIC HEALTH RELEVANCE: A better understanding of short-term changes in functional limitations and disability, and of the impact of risk factors on disability development during chemotherapy in older hormone-refractory prostate cancer patients may be helpful in developing more effective interventions to prevent or reduce disability development, thereby improving public health. The proposed study will examine changes in functional limitations and disability, and relationships over time between biologic and social risk factors and changes in disability.