The purpose of this study was to evaluate novel inflammatory and nutritional prognostic factors in patients with advanced colorectal cancer (ACRC). All ACRC patients attending the clinic for palliative treatment were eligible for study. Demographics, including performance status (PS), C-reactive protein (CRP), albumin (Alb), Glasgow prognostic score (GPS), weight, weight history, body mass index (BMI), and nutritional status using the patient-generated subjective global assessment (PGSGA), were collected and correlated with survival. At a median follow-up of 29.8 mo, with a minimum follow-up of 15.7 mo, the median survival was 9.9 mo (0.8-21.8 mo). Fifteen (29%) patients were newly diagnosed (stage IV colorectal cancer), and 36 (71%) had received prior chemotherapy. Although the median BMI was 27 kg/m2 (range = 17-41 kg/m2), 28 of 50 (56%) were nutritionally at risk. In fact, 19 patients (38%) were critically in need of nutrition intervention (PGSGA score of > or =9). Thirty-three of 48 patients (69%) had an elevated CRP (>10 mg/l with a median of 21.1 mg/L), and 7 patients (15%) had both a CRP of >10 mg/l and hypoalbuminemia (< 35 g/l). A significant positive correlation was found between PGSGA score and CRP (P = 0.003; r = 0.430). Using univariate analysis, significantly worse survival was found for patients with poorer PS (P = 0.001), high GPS (P = 0.04), low Alb (P = 0.017), elevated serum alkaline phosphatase (SAP; P = 0.018), PGSGA score of > 9 (P = 0.001), and PGSGA group B/C (P = 0.02). Using the Cox proportional hazard model for multivariate survival analysis, type of treatment (hazard ratio, HR = 1.48; 95% confidence interval, CI = 1.11-1.79; P = 0.005), PS (HR = 2.37; 95% CI = 1.11-5.09; P = 0.026), GPS (HR = 2.27; 95% CI = 1.09-4.73; P = 0.028), and SAP (HR = 0.44; 95% CI = 0.18-1.07; P =0.069) remained significant predictors of survival. These preliminary data suggest that the type of treatment, PS, GPS, and SAP are important predictors of survival in ACRC.