Reducing Chemotherapy Toxicity in Older Adults

项目简介：超过60%的癌症发生在老年人身上，随着人口老龄化，预计老年癌症患者的数量将会增加。老年癌症患者出现治疗并发症的风险增加，并且没有降低化疗毒性的标准方法。包括癌症和衰老研究小组（CARG）对500名患者的研究在内的几项研究表明，50%的老年患者在治疗开始后3个月内出现化疗严重毒性，老年评估（GA）是一种评估老年人健康状况的有效方法，可以预测严重的化疗毒性。尽管老年评估有很大的潜力来改善老年癌症患者的不良后果，但大多数肿瘤学家还没有采用遗传分析，很大程度上是因为缺乏如何最好地将遗传分析纳入临床护理的知识。本研究的总体假设是，为肿瘤学家提供老年患者的老年评估信息和GA指导下的有针对性的干预措施，可以降低化疗毒性的风险。首席研究员是一名老年肿瘤学家，通过CARG组建的研究团队有能力成功完成这项高影响力的研究。这项研究将分两个阶段进行。在第一阶段，70岁及以上的转移性恶性实体瘤患者（n=240）计划在罗切斯特大学社区临床肿瘤项目（CCOP）接受一线化疗，将在1年的时间内招募。“常规护理”实践包括医生特征、处方模式、患者和医生对化疗开始的决策以及化疗毒性将被捕获。在第二阶段，我们将利用CCOP位点进行一项双臂随机研究。在化疗开始前，70岁及以上（n=688）的转移性恶性实体瘤患者将完成GA。随机分配到第1组的肿瘤学家将收到GA结果的摘要以及考虑实施的靶向干预措施。在第二组中，肿瘤学家将仅从GA获得关于严重抑郁或认知障碍的信息。主要结果将是在化疗开始后3个月出现严重化疗毒性的患者比例的比较。次要结果将包括生存率的比较，两组实施的干预措施数量，以及化疗的决策。一个探索性的目的是评估GA加靶向干预是否可以减缓老年晚期癌症患者的功能和身体衰退。关于预期结果，该建议将填补关于GA是否可以改善老年癌症患者的结果以及GA如何改善生活质量的机制（决策，GA驱动的干预）方面的重要知识空白。这些数据将提供一种实用的机制，将GA纳入常规临床肿瘤治疗，以改善老年转移性癌症患者的预后。

DESCRIPTION (provided by applicant): Project Summary: Over 60% of cancers occur in older persons, and the number of older cancer patients is expected to grow as the population ages. Older cancer patients are at increased risk of treatment complications, and there is no standard approach for reducing chemotherapy toxicity. Several studies, including a Cancer and Aging Research Group (CARG) study in 500 patients, have demonstrated that 50% of older patients have severe toxicity from chemotherapy within 3 months of treatment initiation and that measures within a geriatric assessment (GA), a validated approach to assessing health status in older persons, can predict severe chemotherapy toxicities. Although geriatric assessment has great potential to improve adverse outcomes of older adults with cancer, the majority of oncologists have not adopted GA, largely because of lack of knowledge on how to best incorporate GA into clinical care. The overall hypothesis of this proposed research is that providing oncologists with information from geriatric assessment with and targeted interventions guided by GA for older patients can reduce the risk of chemotherapy toxicity. The principal investigator, a geriatric oncologist, and the research team assembled through CARG are well positioned to successfully complete this high-impact research. The study will be conducted in 2 phases. In Phase 1, patients aged 70 and over (n=240) with metastatic solid tumor malignancies who are planning to receive first-line chemotherapy at University of Rochester Community Clinical Oncology Program (CCOP) sites will be recruited over the course of 1 year. "Usual-care" practices including physician characteristics, prescribing patterns, patient and physician decision-making for chemotherapy initiation, and chemotherapy toxicity will be captured. In Phase 2, we will conduct a 2-armed cluster randomized study utilizing CCOP sites. Prior to chemotherapy initiation, patients aged 70 and over (n=688) with metastatic solid tumor malignancies will complete a GA. The oncologists at sites randomized to Arm 1 will receive a summary of GA results plus targeted interventions to consider for implementation. In Arm 2, oncologists will only receive information from GA regarding severe depression or cognitive impairment. The primary outcome will be a comparison of the proportion of patients who have severe chemotherapy toxicity at 3 months after chemotherapy initiation. Secondary outcomes will include comparisons of survival, the number of interventions implemented in both groups, and decision-making for chemotherapy. An exploratory aim will evaluate whether or not GA plus targeted interventions can slow functional and physical decline in older patients with advanced cancer. With regard to expected outcomes, this proposal will fill vital gaps in knowledge regarding whether GA can improve outcomes of older cancer patients and the mechanisms of how GA can improve quality of life (decisions, GA-driven interventions). These data will have a positive impact by providing a pragmatic mechanism for incorporating GA into routine clinical oncology care to improve outcomes of older adults with metastatic cancer.