Predictors of Short-Term Survival and Progression to Chemotherapy in Patients With Advanced Colorectal Cancer Treated With 5-Fluorouracil-Based Regimens

Abstract

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.

New insights into the role of age and carcinoembryonic antigen in the prognosis of colorectal cancer

“…Thus, different age ranges of the populations studied, or different age groups chosen for the analyses, together with a variable prevalence of nonneoplastic diseases in the evaluated series, can explain the discordant results in the scientific literature regarding age and colorectal cancer. Indeed, different authors have found an independent unfavourable effect of increasing age (Korenaga et al, 1991;Gasser et al, 1992;Crocetti et al, 1996;D'Eredita et al, 1996;Wolters et al, 1996;Payne and Meyer, 1997;Tominaga et al, 1997;Heys et al, 1998;Lagautriere et al, 1998;Fietkau et al, 2004;Munemoto et al, 2004), of the youngest and oldest age ranges, indifferently (Chung et al, 1998;Cerottini et al, 1999;Massacesi et al, 2002) or even of young age (Cai et al, 2005), while other investigators were not able to demonstrate any prognostic effect at all (Ponz de Leon et al, 1992;Wang et al, 2000;Mitry et al, 2004;Latkauskas et al, 2005). Only JanssenHeijnen et al (2005) evaluated relative survival of patients with several cancers, utilising data from the Southern Netherlands Cancer Registry.…”

Prognostic factors in patients with recently diagnosed incurable cancer: a systematic review

“…Age was associated with survival duration in some studies, but the direction of effect was inconsistent. Most studies used a single cut-off between 60 and 70 years, which would be suitable for [31][32][33][34][35][36][37], breast [38,39], pancreas [44][45][46][47], urothelial [48,49,51,52], gastric [54], GI [55,56], oesophageal [58], prostate [59], melanoma [61], renal [63] Lung Trial outcome index=sum of physical well being, functional well being and lung cancer subscale of the FACT-L. Egogram=Tokyo University Egogram (scores 5 ego state factors: critical parent, nurturing parent, adult, free child and adapted child) UV Univariable analysis, MV multivariable analysis, KPS Karnovsky performance score, ECOG Eastern Cooperative Oncology Group performance score monotonic effects; for example, better survival in younger (or older) patients but would miss U-shaped relationships or if prognosis was better in typical middle-aged patients but worse in the youngest and oldest. Co-morbidity seems more important than age.…”

“…Formal meta-analysis was neither planned nor attempted because the populations, methods and reported results were too heterogeneous. [32][33][34][35], pancreas [44][45][46][47], urothelial [48,51,52], gastric [53,54], GI [55,56], oesophageal [58], renal [63] Male worse [31,33,34], breast [38,40], pancreas [43,44,46,47] , urothelial [48,51,52] gastric [53,54], GI [56], oesophageal [58], ovary [62], renal [63] Younger …”

Apoptotic Index and bcl-2 Expression as Prognostic Factors in Colorectal Carcinoma

“…CEA elevation correlates with the degree of tumor differentiation, and patients with poorly differentiated tumors can sometimes have normal tests despite significant tumor volume [31]. In general, however, CEA correlates with stage of disease and is elevated most strikingly in the plasma of patients with hepatic metastases [32, 33]. …”