New utility of an old marker: serial alpha-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy.
OBJECTIVE
There are limitations in using radiologic evaluation to assess the treatment outcome of patients with hepatocellular carcinoma (HCC). The use of serial alpha-fetoprotein (AFP) in monitoring response has not been rigorously evaluated. We aimed to study the clinical value of AFP trend in an attempt to validate AFP as a surrogate serologic end point.


METHODS
Participants from a phase III randomized trial of systemic chemotherapy in HCC were studied. Serum AFP was prospectively collected in parallel with clinical and radiologic outcome. AFP response was defined as a decrease in AFP of more than 20% after a minimum of two cycles of chemotherapy. We studied the relationship between AFP response and treatment outcome in terms of radiologic response and overall survival.


RESULTS
Of 188 patients, 117 patients with elevated serum AFP (> 20 microg/L) and documented radiologic evaluation had received at least two cycles of chemotherapy. A total of 47 AFP responders were identified. AFP responders had better survival than nonresponders (13.5 v 5.6 months, respectively; P < .0001), and AFP response was strongly associated with radiologic response (P < .0001). Multivariate analysis suggested that AFP response was significantly associated with survival (hazard ratio, 0.413; 95% CI, 0.273 to 0.626; P < .0001). AFP responses were frequently observed in patients with radiologically stable disease (SD) and tended to identify a subgroup of SD patients with better survival.


CONCLUSIONS
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.
Chan
Stephen L
SL
Department of Clinical Oncology, State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Hong Kong Cancer Institute and Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.
Mo
Frankie K F
FK
Johnson
Philip J
PJ
Hui
Edwin P
EP
Ma
Brigette B Y
BB
Ho
Wing M
WM
Lam
Kwok C
KC
Chan
Anthony T C
AT
Mok
Tony S K
TS
Yeo
Winnie
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D011379:Prognosis; D011446:Prospective Studies; D011859:Radiography; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis*
D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins