Impact of Young Age on Treatment Efficacy and Safety in Advanced Colorectal Cancer: A Pooled Analysis of Patients From Nine First-Line Phase III Chemotherapy Trials
Impact of Young Age on Treatment Efficacy and Safety in Advanced Colorectal Cancer: A Pooled Analysis of Patients From Nine First-Line Phase III Chemotherapy Trials
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DOI：
10.1200/jco.2010.33.5281
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发表时间：
2011-07-10
影响因子：
45.3
通讯作者：
Sargent, Daniel J.
中科院分区：
文献类型：
--
作者：
Blanke, Charles D.;Bot, Brian M.;Sargent, Daniel J.
目的结直肠癌主要发生在老年人，但约5%的患者年龄在50岁或以下。我们试图确定年轻年龄是否对晚期疾病患者的预后有影响，或者是否影响化疗的疗效/毒性。方法我们分析了使用基于氟尿嘧啶的单药和联合化疗的9项晚期结直肠癌(ACRC)III期试验中6,284名患者的个人数据。终点包括无进展生存期(PFS)、总生存期(OS)、反应率(RR)和3级或更严重的不良事件。结果793例(13%)患者年龄在50岁以下，其中188例(3%)患者年龄在40岁以下。3级或更严重的恶心(10%比7%；P=.01)更常见，严重腹泻(11%比14%；P=.001)和中性粒细胞减少症(23%比26%；P<；.001)在年轻(50岁以下)患者中比老年(50岁以上)患者少见。年龄是PFS的预后因素，50岁以下的患者预后较差(中位数，6.0个月比7.5个月；风险比1.10；P=0.02)，但不影响RR或OS。在单一治疗和联合化疗试验的子集中，多药化疗对年轻和老年患者的相对益处是相似的。在使用40岁的年龄切割点时，结果具有可比性。结论在接受治疗的ACRC患者中，年轻与较差的PFS略有关联，但与OS或RR无关，而且年轻患者总体上有更多的恶心但较少的腹泻和中性粒细胞减少症。年轻患者与老年患者从联合化疗中获得相同的好处。在没有临床试验结果的情况下，标准的联合化疗方法适用于年轻的ACRC患者。
PurposeColorectal cancer predominantly occurs in the elderly, but approximately 5% of patients are 50 years old or younger. We sought to determine whether young age is prognostic, or whether it influences efficacy/toxicity of chemotherapy, in patients with advanced disease.MethodsWe analyzed individual data on 6,284 patients from nine phase III trials of advanced colorectal cancer (aCRC) that used fluorouracil-based single-agent and combination chemotherapy. End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events. Stratified Cox and adjusted logistic-regression models were used to test for age effects and age-treatment interactions.ResultsA total of 793 patients (13%) were younger than 50 years old; 188 of these patients (3% of total patients) were younger than 40 years old. Grade 3 or worse nausea (10% v 7%; P = .01) was more common, and severe diarrhea (11% v 14%; P = .001) and neutropenia (23% v 26%; P < .001) were less common in young (younger than 50 years) than in older (older than 50 years) patients. Age was prognostic for PFS, with poorer outcomes occurring in those younger than 50 years (median, 6.0 v 7.5 months; hazard ratio, 1.10; P = .02), but it did not affect RR or OS. In the subset of monotherapy versus combination chemotherapy trials, the relative benefits of multiagent chemotherapy were similar for young and older patients. Results were comparable when utilizing an age cut point of 40 years.ConclusionYoung age is modestly associated with poorer PFS but not OS or RR in treated patients with aCRC, and young patients have more nausea but less diarrhea and neutropenia with chemotherapy in general. Young versus older patients derive the same benefits from combination chemotherapy. Absent results of a clinical trial, standard combination chemotherapy approaches are appropriate for young patients with aCRC.