Alpha-Fetoprotein Response in Advanced Hepatocellular Carcinoma Receiving Cytostatic Agent
Authors: Li-Tzong Chen, Her-Shyong Shiah, Yee Chao, Jang-Yang Chang, Li-Ting Cheng, Jacqueline Whang-Peng
Journal: Journal of Clinical Oncology (2009)

We read with interest the article by Chan et al 1 in which they showed that ␣-fetoprotein (AFP) response is an independent prognostic factor for overall survival in patients with advanced hepatocellular carcinoma (HCC) receiving systemic doxorubicinbased chemotherapy.Chan et al also suggested the incorporation of AFP response into the criteria evaluating treatment outcome of advanced HCC in clinical practice and future clinical trials.We had reached similar conclusions based on a study in HCC patients receiving thalidomide, an antiangiogenic compound, in 2005. 2 In the study by Chan et al, 1 patients with elevated baseline AFP (Ͼ 20 g/L) were included, and AFP response was defined as a more than 20% decrease in AFP serum level after two to three cycles of doxorubicin-based chemotherapy.Discordance between AFP and radiographic responses were observed in 18.5% (five of 27) and 8.9% (four of 45) of patients with WHO criteria-defined objective response and progressive disease, respectively. 1The etiology for the discrepancy was attributed to the increase of AFP secondary to hepatitis B virus reactivation in two, relatively low baseline AFP level (28 to 81 g/L) in three, and unknown in four patients.Based on these observations, Chan et al warned that one should exercise caution when applying AFP response in HCC patients with either active hepatitis or a relatively low baseline AFP level.Conversely, with more stringent patient selection and AFP response criteria, the discrepancy between AFP and standard radiographic responses was a minor issue in our thalidomide study, in which AFP response was defined as a 50% or more decrease of AFP serum level for 4 or more weeks during therapy. 2 In addition, to avoid the influence of non-tumor-originating AFP elevations (ie, those associated with hepatitis activity), only patients with baseline AFP serum level above 200 g/L were included. 2,3Among the 42 enrolled patients, AFP response was observed in 100% (three of three), 43% (six of 14), and 4% (one of 25) of patients with radiographic partial response, stable disease, and progressive disease (by WHO criteria as well), respectively.The only AFP responder with radiographic progressive disease actually had a mixed tumor response-a significant reduction of total tumor burden with a more than 25% increase in size of one minor lesion.The results of the two studies suggest the potential use of AFP tumor marker response as a surrogate marker per se or as an adjunct to radiographic response in evaluating the therapeutic efficacy of systemic cytotoxic and/or cytostatic therapy in advanced HCC.Incorporation of AFP response into the criteria evaluating treatment outcome appears to be more critical for clinical trials involving novel, molecular-targeted agents in HCC because most of the compounds are cytostatic and are expected to achieve disease stabilization rather than objective response by radiographic measurement.In such instances, serial AFP monitoring may more accurately reflect the biologic response of advanced HCC than radiographic measurement can. 2 However, definition of AFP response should be standardized through a consensus meeting and further validated in prospective clinical trials before it can be incorporated as a reliable end point in future HCC trials.