Peroxisome proliferator-activated receptor-gamma and cyclooxygenase-2 are frequently overexpressed on cholangiocarcinoma (CC) cells and adjacent stroma cells, and might be potential therapeutic targets. A pilot phase II trial was started to analyze the activity of angiostatically scheduled chemotherapy, capecitabine 2 × 1 g/m2from day 15 to 28 every 3 weeks combined with an antiinflammatory/angiostatic therapy, daily 45 mg oral pioglitazone and 25 mg oral rofecoxib day 1+ in advanced CC. All 21 consecutively included patients (mean age 64 years) suffered from non-resectable far-advanced CC, 62% were pretreated. The median dose of capecitabine per cycle was 76% of that planned; the median duration of treatment was 6.8 months (range 2 to 30+). Only three patients suffered from grade 3 toxicity (hand-foot syndrome n = 2, edema n = 1). Therapy continuation was refused in one patient with HFS grade 3. Objective response was achieved in 29% of the cases including one cCR, 29% achieved SD >6 months. Median overall survival was 8 months. The median overall survival in this unselected, partially pretreated patient population compares to that observed in selected patient populations receiving second generation combination chemotherapies which were shown to be accompanied with considerable hematotoxicity. The present completely oral therapy approach combines convenience, low toxicity and efficacy, and fits to the general patients characteristics: elderly patients with tumor-associated comorbidity. Randomized trials will definitely clarify the impact of antiinflammatory treatment strategies on survival.