Massacesi Cristian, Pistilli Barbara, Valeri Michele, Lippe Paolo, Rocchi Marco B L, Cellerino Riccardo, Piga Andrea
Department of Medical Oncology, University of Ancona, Ancona, Italy.
Am J Clin Oncol. 2002 Apr;25(2):140-8. doi: 10.1097/00000421-200204000-00008.
The aim of this study was to assess in patients with advanced colorectal cancer which factors were associated with short-term survival (6 months or less) and progression to first-line 5-fluorouracil (5-FU) chemotherapy. Three hundred twenty-one consecutive nonselected patients with advanced colorectal cancer were treated with conventional 5-FU-based regimens as first-line treatment from 1988 to 1999. Factors related to patient, tumor, or treatment were analyzed by univariate and multivariate logistic regression analysis by comparing short survivors (SS, those who survived <or=6 months) with those who survived longer than 6 months. The same statistical methods were used to analyze 200 patients, all treated with bolus 5-FU regimens, by comparing who progressed to treatment with those who did not. Sixty-two patients (19.3%) were SS, the remaining 259 patients survived more than 6 months. First-line chemotherapy included 5-FU in all patients; 112 (35%) and 27 (8.4%) patients were offered, after disease progression, second and third-line chemotherapy, respectively. The overall response rate to first-line chemotherapy was 12.9%. No SS patient achieved an objective response. To investigate factors associated with progression to first-line chemotherapy, we considered only those patients treated with bolus 5-FU regimens, to eliminate the variable of regimen used. Ninety-six of them progressed to treatment and 104 did not. At multivariate analysis, SS patients were characterized by the following: right and transverse colon primary (p = 0.006), younger age (p = 0.043), poor performance status (Eastern Cooperative Oncology Group >or= 2) (p = 0.015), elevated (>or=5 microg/l) serum carcinoembryonic antigen (CEA) (p = 0.015), and more than one site of metastatic disease (p < 0.001). Progression to first-line chemotherapy (p < 0.001) was also a strong factor associated with short survival in multivariate analysis; factors predictive of progression were elevated CEA (p = 0.027) and diffuse metastatic disease (p = 0.029). Our data indicate the relevance of some clinical prognostic factors (younger age, poor performance status, elevated CEA, site of primary, number of metastatic sites, resistance to chemotherapy) as independent factors associated with poor survival and progression to first-line chemotherapy in patients with metastatic colorectal cancer treated with conventional 5-FU regimens. Patients identified by these factors as having a poor prognosis and low probability of response to treatment should be considered either for more aggressive regimens or supportive care only: conventional 5-FU treatments do not impact on response or survival.
本研究的目的是评估晚期结直肠癌患者中哪些因素与短期生存（6个月或更短时间）以及进展至一线5-氟尿嘧啶（5-FU）化疗相关。1988年至1999年，321例连续入选的晚期结直肠癌患者接受了以传统5-FU为基础的方案作为一线治疗。通过单因素和多因素逻辑回归分析，比较短期生存者（SS，即生存时间≤6个月者）与生存时间超过6个月者，分析与患者、肿瘤或治疗相关的因素。采用相同的统计方法对200例均接受5-FU推注方案治疗的患者进行分析，比较进展至治疗者与未进展者。62例患者（19.3%）为短期生存者，其余259例患者生存时间超过6个月。所有患者的一线化疗均包含5-FU；疾病进展后，分别有112例（35%）和27例（8.4%）患者接受了二线和三线化疗。一线化疗的总缓解率为12.9%。没有短期生存者获得客观缓解。为研究与进展至一线化疗相关的因素，我们仅考虑接受5-FU推注方案治疗的患者，以消除所用方案这一变量的影响。其中96例进展至治疗，104例未进展。多因素分析显示，短期生存者具有以下特征：右半结肠和横结肠原发（p = 0.006）、年龄较轻（p = 0.043）、体能状态差（东部肿瘤协作组≥2）（p = 0.015）、血清癌胚抗原（CEA）升高（≥5μg/l）（p = 0.015）以及转移病灶超过一处（p < 0.001）。在多因素分析中，进展至一线化疗（p < 0.001）也是与短期生存相关的一个重要因素；预测进展的因素为CEA升高（p = 0.027）和弥漫性转移疾病（p = 0.029）。我们的数据表明，一些临床预后因素（年龄较轻、体能状态差、CEA升高、原发部位、转移部位数量、化疗耐药）作为独立因素，与接受传统5-FU方案治疗的转移性结直肠癌患者生存不良和进展至一线化疗相关。被这些因素确定为预后不良且对治疗反应可能性低的患者，应考虑采用更积极的方案或仅给予支持治疗：传统5-FU治疗对反应或生存无影响。
