Impact of biomarkers on disease survival and progression in patients treated with octreotide for advanced hepatocellular carcinoma.
BACKGROUND
Current determination of prognosis for advanced hepatocellular carcinoma (HCC) is mainly based on clinical assessment. We aimed to determine the impact of biomarkers as predictive factors for HCC progression and survival during octreotide-based treatments.


METHODS
We included patients who had been prospectively randomised to receive either octreotide (30 mg) alone monthly (n = 39) or in combination with rofecoxib (up to 50 mg bid daily, n = 32) for a minimum of 6 months, or until death occurred.


RESULTS
Overall median survival (154 days) and median time to progression (94 days) were not different for both treatments and the biomarkers investigated (VEGF-A, IGF-1, PGE-2, ET-A) were similarly distributed amongst treatment groups. Combined univariate group analysis revealed that survival was decreased for an uptake ratio of > 2 on initial octreoscan (P = 0.05); baseline serum VEGF-A and IGF-1 were further significantly associated with survival. On multivariate analysis, uncorrected serum VEGF-A appeared to be the most significant predictor for tumor progression and survival.


CONCLUSIONS
Biomarkers, in addition to established tumor markers, are independent predictors of tumor progression and survival in patients with advanced HCC treated with octreotide. Furthermore, the involvement of VEGF-A implies the inhibition of angiogenesis as a potential mechanism of action for this drug.
Treiber
G
G
Department of Gastroenterology and Hepatology, University Hospital of Magdeburg, Magdeburg, Germany. ingtre@uniklinikum-saarland.de
Wex
T
T
Röcken
C
C
Fostitsch
P
P
Malfertheiner
P
P
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D015232:Dinoprostone / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007783:Lactones / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D015282:Octreotide / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D013450:Sulfones / Q000008:administration & dosage; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D014408:Biomarkers, Tumor; D007783:Lactones; D013450:Sulfones; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C116926:rofecoxib; D007334:Insulin-Like Growth Factor I; D015232:Dinoprostone; D015282:Octreotide