University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
J Clin Oncol. 2011 Jul 10;29(20):2781-6. doi: 10.1200/JCO.2010.33.5281. Epub 2011 Jun 6.
Colorectal 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.
We 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.
A 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.
Young 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.
结直肠癌主要发生在老年人中，但约有 5%的患者年龄在 50 岁以下。我们旨在确定年轻是否具有预后意义，或者它是否会影响晚期疾病患者化疗的疗效/毒性。
我们分析了来自氟尿嘧啶为基础的单药和联合化疗的 9 项晚期结直肠癌（aCRC）III 期临床试验的 6284 名患者的个体数据。终点包括无进展生存期（PFS）、总生存期（OS）、缓解率（RR）和 3 级或更高级别的不良事件。分层 Cox 和调整后的逻辑回归模型用于检验年龄效应和年龄-治疗相互作用。
共有 793 名患者（13%）年龄小于 50 岁；其中 188 名患者（总患者的 3%）年龄小于 40 岁。3 级或更高级别的恶心（10%比 7%；P =.01）更为常见，而严重腹泻（11%比 14%；P =.001）和中性粒细胞减少（23%比 26%；P <.001）在年轻（小于 50 岁）患者中比在年老（大于 50 岁）患者中更少见。年龄对 PFS 具有预后意义，年龄小于 50 岁的患者预后较差（中位数，6.0 比 7.5 个月；风险比，1.10；P =.02），但对 RR 或 OS 没有影响。在单药与联合化疗试验的亚组中，联合化疗的相对益处在年轻和年老患者中相似。当使用 40 岁的年龄切点时，结果是可比的。
在接受治疗的 aCRC 患者中，年轻与较差的 PFS 适度相关，但与 OS 或 RR 无关，并且年轻患者在接受化疗时通常会出现更多的恶心，但腹泻和中性粒细胞减少较少。年轻患者从联合化疗中获得相同的益处。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。
