AFP, AFP-L3% and DCP levels in patients with advanced hepatocellular carcinoma treated with sorafenib

Background: Patients suffering from advanced hepatocellular carcinoma (HCC) have a dismal prognosis with survival rates of less than six months. The multikinase inhibitor sorafenib (Nexavar®) was recently approved for the treatment of advanced HCC providing survival benefit (Llovet, NEJM, 2008). Considering the shortcomings of RECIST criteria in the age of targeted therapy we have investigated serum levels of alpha-Fetoprotein (AFP), AFP-L3% (fraction of AFP binding to Lens culinaris agglutinin) and des-gamma-carboxy-prothrombin (DCP, PIVKA-II) as potential markers for response to sorafenib treatment. Methods: 49 patients (pts) in our HCC outpatient clinic were treated with the standard dose of 400mg sorafenib twice daily from January 2007 to August 2008. In 26 pts, AFP-L3% and DCP levels were measured by the Liquid-phase Binding Assay System™ (Wako Chemicals GmbH) before treatment. In 15 of these pts, parameters were also measured in the course of sorafenib treatment. The control group comprised 55 pts with liver cirrhosis but no evidence of HCC. Results: Levels of DCP, AFP and AFP-L3% were significantly elevated in HCC pts before sorafenib treatment (AFP >10ng/ml: 21/26 (81%), AFP-L3 >10%: 18 of 21 AFP-positive pts (86%); DCP >7.5ng/ml: 23/26 (88%). In control pts AFP, AFP-L3% and DCP were elevated in 2/55 (3.6%), 0/55 and 7/55 (13%), respectively. A reduction of elevated AFP-/AFP-L3% and DCP during therapy was observed in 9/21 (43%), 11/18 (61%) and 12/23 (52%), respectively. Interestingly, in pts with AFP reduction during therapy, DCP increased in 5/9 (56%). In pts with AFP increase, DCP increased in 6/12 (50%). Survival time of pts with DCP or AFP increase was shorter compared to those with a concomitant decrease of both parameters. Conclusion: Monitoring of AFP, AFP-L3% and DCP may provide a readily available marker combination to assess response to sorafenib treatment.