Obeidat Nour A, Pradel Françoise G, Zuckerman Ilene H, DeLisle Sylvain, Mullins C Daniel
Pharmaceutical Health Services Research Department, University of Maryland, Baltimore, Maryland, USA.
Am J Geriatr Pharmacother. 2009 Dec;7(6):343-54. doi: 10.1016/j.amjopharm.2009.11.005.
Several population-based studies have confirmed the benefits of adjuvant chemotherapy with 5-fluorouracil/leucovorin for treatment of colorectal cancer. Few population-based studies have evaluated other chemotherapies that are now available for colorectal cancer management.
This study primarily sought to evaluate the survival benefit of first-line irinotecan use in a group of Medicare patients with stage IV (metastatic) colorectal cancer.
Data on chemotherapy users with a diagnosis of colorectal cancer reported between 1998 and 2002 were obtained from the Surveillance Epidemiology and End Results (SEER)-Medicare database. Irinotecan, marketed in 1997, was one of the newer chemotherapy agents in the available data. Chemotherapy episodes, defined as periods of continuous chemotherapy treatment with no gaps >90 days between successive claims, were identified. The first chemotherapy episode after diagnosis was used to identify lines of treatment: patients may have initiated irinotecan therapy within 2 months (first-line), used irinotecan later in the first episode (second-line), or not used irinotecan at all. Descriptive statistics were generated and a multivariable Cox proportional hazards model was used to determine the survival benefit of irinotecan. Secondary analyses explored the survival benefit in specific patient subgroups. The impact of irinotecan use on health care utilization also was assessed.
Of 3327 chemotherapy users (mean/median age, 75 years), 842 (25.3%) initiated chemotherapy using irinotecan. No overall survival benefit for irinotecan was observed in the primary analysis comparing irinotecan initiators with all other chemotherapy users (including those who used irinotecan subsequently). Covariates that were negatively associated with survival included older age, presence of >1 comorbidity, a high tumor grade, lymph node involvement, and a primary tumor site in the colon. Surgery was positively associated with a lower hazard of death. In subgroup analyses that excluded subsequent irinotecan users, a survival benefit for irinotecan was observed but diminished over time. Irinotecan users had higher rates of hospitalizations possibly due to chemotherapy-related adverse effects. This retrospective claims study had limitations such as a lack of information on patient performance status, dosing, and the types of regimens used; hence, certain assumptions had to be made and selection bias may have been involved.
The definitive survival advantage of irinotecan observed in clinical trials was not reproducible in this population of elderly Medicare patients. The results emphasize the need for expansion of trials to include a more diverse patient group as well as continued evaluation of more recent chemotherapies in real-world settings.
多项基于人群的研究已证实，氟尿嘧啶/亚叶酸钙辅助化疗对治疗结直肠癌有益。很少有基于人群的研究评估目前可用于结直肠癌治疗的其他化疗方法。
本研究主要旨在评估一线使用伊立替康对一组患有IV期（转移性）结直肠癌的医疗保险患者的生存获益情况。
从监测、流行病学和最终结果（SEER）-医疗保险数据库中获取1998年至2002年期间报告的诊断为结直肠癌的化疗使用者的数据。伊立替康于1997年上市，是现有数据中较新的化疗药物之一。确定化疗疗程，定义为连续化疗治疗期，连续索赔之间无超过90天的间隔。诊断后的第一个化疗疗程用于确定治疗线：患者可能在2个月内开始使用伊立替康治疗（一线），在第一个疗程后期使用伊立替康（二线），或根本未使用伊立替康。生成描述性统计数据，并使用多变量Cox比例风险模型确定伊立替康的生存获益。二次分析探讨了特定患者亚组中的生存获益情况。还评估了使用伊立替康对医疗保健利用的影响。
在3327名化疗使用者（平均/中位年龄75岁）中，842名（25.3%）开始使用伊立替康进行化疗。在将伊立替康起始者与所有其他化疗使用者（包括随后使用伊立替康的使用者）进行比较的初步分析中，未观察到伊立替康对总生存的获益。与生存呈负相关的协变量包括年龄较大、存在>1种合并症、肿瘤分级高、淋巴结受累以及结肠原发性肿瘤部位。手术与较低的死亡风险呈正相关。在排除随后使用伊立替康的使用者的亚组分析中，观察到伊立替康有生存获益，但随着时间推移而减弱。伊立替康使用者因化疗相关不良反应导致住院的发生率较高。这项回顾性索赔研究存在局限性，例如缺乏关于患者体能状态、剂量和所用方案类型的信息；因此，不得不做出某些假设，可能存在选择偏倚。
在临床试验中观察到的伊立替康明确的生存优势在这群老年医疗保险患者中无法重现。结果强调需要扩大试验，纳入更多样化的患者群体，并继续在现实环境中评估更新的化疗方法。
