Predictors of short-term survival and progression to chemotherapy in patients with advanced colorectal cancer treated with 5-fluorouracil-based regimens.

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.