Evaluation of predictive markers for patients with advanced colorectal cancer

Background. To evaluate the predictive and prognostic value of serum and plasma tumor markers, in comparison with clinical and biomedical parameters for response rate (RR), progression-free survival (PFS) and overall survival (OS) among patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy. Material and methods. One-hundred and six patients with mCRC from three centers, part of a multicenter study, received irinotecan with the Nordic bolus 5-fluorouracil (5-FU) and folinic acid schedule (FLIRI) or the de Gramont schedule (Lv5FU2-IRI). Blood samples for CEA, CA19-9, TPA, TIMP-1, SAA, transthyretin and CRP were taken at baseline and after two, four and eight weeks of treatment. Tumor marker levels at baseline and longitudinally were compared with responses evaluated (CT/MRI) after two and four months of treatment. The correlations to RR, PFS and OS were evaluated with regression analyses. Results. A significant correlation to OS was seen for baseline levels of all markers. In multivariate analyses with clinical parameters, TPA, CRP, SAA and TIMP-1 provided independent information. The baseline values of CEA, TPA and TIMP-1 were also significantly correlated to PFS and TPA to RR. Changes during treatment, i.e. the slope gave with the exception of CA19-9 for OS less information about outcomes. The best correlation to response was seen for CEA, CA19-9 and TPA with AUC values of 0.78, 0.83 and 0.79, respectively, using a combined model based upon an interaction between the slope and the baseline value. Conclusions. Baseline tumor markers together with clinical parameters provide prognostic information about survival in patients with mCRC. The ability of the individual tumor markers to predict treatment response and PFS is limited. Changes in marker levels during the first two months of treatment are less informative of outcome.