Anti-inflammatory therapy combined with angiostatic scheduling of chemotherapy in advanced biliary tract cancer, hepatocellular carcinoma and gastric cancer

Abstract

4175 Background:Chronic inflammatory processes are involved in carcinogenesis and promotion of liver (HCC), cholangiocellular (CCC) and gastric cancer (GC). Methods: A pilot trial was started to analyze the activity of angiostatic scheduled chemotherapy, capecitabine 2 x 1 g/m2 from day 14 to 28 every 3 weeks, combined with an anti-inflammatory therapy (daily 45 mg pioglitazone po and 25 mg rofecoxib po) in advanced CCC, HCC and GC. Results: Fifteen patients (pts) with CCC, 5 pts with HCC and 13 pts with GC were evaluable (preceding chemotherapies in CCCs and HCCs/ GCs: mean 0.35/1.3, range 0 to 3/ 1 to 3). Major side effects (WHO grade 3 to 4) were due to capecitabine treatment. Therapy was stopped in 2 cases due to hand-foot syndrome. Objective responses were observed in CCC 20%, HCC 20%, and GC 15% including CR in 3 pts (CCC, n=1, one marker-negative CR in HCC, GC, n=1), PR in 2 pts with CCC and 1 pt with GC. Additional 8 pts (24%) achieved disease stabilization (SD) lasting >6 months (CCC, n=6, HCC, n=1, GC n=1). Overall clinical benefit occurred in 42% (CR/PR/SD). Median progression-free survival has not been reached in CCC at a median observation time of 12.1 months, was 3.2 months in HCC, and 3 months in GC. Conclusions: The new combined all-oral anti-inflammatory and metronomic chemotherapy is remarkably well tolerated in advanced HCC, CCC and GC and may induce CR as well as prolonged disease stabilization even in pre-treated pts. Therefore, the present combination therapy reveals further evaluation. No significant financial relationships to disclose.