New Utility of an Old Marker: Serial α-Fetoprotein Measurement in Predicting Radiologic Response and Survival of Patients With Hepatocellular Carcinoma Undergoing Systemic Chemotherapy

Abstract

Serial AFP measurement is useful in prognostication and monitoring treatment response in HCC patients undergoing systemic chemotherapy. Incorporation of AFP response into the criteria evaluating treatment outcome should be considered in clinical practice and clinical trials of novel agents in HCC.

Serum α-Fetoprotein Response as a Surrogate for Clinical Outcome in Patients Receiving Systemic Therapy for Advanced Hepatocellular Carcinoma

“…They demonstrated that AFP responders had longer OS times than nonresponders, and AFP response was strongly associated with radiologic response [21]. Given the fluctuating nature of AFP measurements in patients with such coexisting conditions as cirrhosis and hepatitis, we chose a relatively high percentage cutoff of 50% so as to capture real changes related to HCC and minimize contributions from background sources and laboratory variations in different assays.…”

“…Another early report, however, showed no correlation between AFP and objective evidence of remission [19]. Recent studies have shown that an AFP decrease correlates with survival benefit from thalidomide [20] and also from two palliative regimens with cisplatin, interferon, doxorubicin, and 5-fluorouracil and with doxorubicin [21].…”

The Significance of Early Alpha-Fetoprotein Level Changes in Predicting Clinical and Survival Benefits in Advanced Hepatocellular Carcinoma Patients Receiving Sorafenib

“…Importantly, in the era of targeted therapy, most of the targeted agents like sorafenib are rather cytostatic than cytotoxic. Thus, the tumor may respond well without significant radiological changes [8,9]. Especially in HCC, it is well known that sorafenib can induce tumor necrosis that can initially manifest as enlarging lesion rather than shrinkage [9].…”

“…Recent studies had demonstrated that serial changes of AFP have an important role in predicting response in advanced HCC receiving chemotherapy [8], thalidomide [11], or a combination of various anti-angiogenic agents with metronomic oral 5-fluoropyrimidine [12]. Nevertheless, single-agent sorafenib is the only compound approved by the U.S. Food and Drug Administration and regulatory authorities worldwide for the management of advanced HCC patients [2].…”

Drug Development for Hepatocellular Carcinoma: Knowing the Past Helps to Understand the Future

“…Its history dates back to the 1980s, and for the past 30 years, potential activities of a wide spectrum of cytotoxic chemotherapeutic agents have been reported by various studies, with doxorubicin as the most commonly used regimen. According to large-scale randomized clinical trials using chemotherapy as first-line systemic treatment, the overall survival of patients undergoing doxorubicin treatment was in the range of 6-7 months, with radiological and serological response rates of around 5% and 20%, respectively [8,9,13]. Unfortunately, there has never been a single prospective randomized study to compare chemotherapy with placebo for treatment of HCC.…”