Impact of different anticancer regimens on biomarkers of angiogenesis in patients with advanced hepatocellular cancer.
OBJECTIVE
Advanced hepatocellular cancer (HCC) is a highly vascularised tumor with limited treatment options. We wanted to evaluate the impact of different treatments on systemic biomarkers linked to angiogenesis.


METHODS
Two subsequent prospective, randomised, phase-I/II trials in patients with advanced HCC were performed. A total of 38 patients was randomised to a total of 4 regimens consisting of 3 cycles of 4 weeks each: Trial 1 included group 1 receiving octreotide 30 mg im on day 1, and group 2 octreotide 30 mg on day 1 plus Imatinib 400 mg po daily; Trial 2 included group 3 with oxaliplatin on day 1 (60 mg-90 mg/m(2)), and group 4 with oxaliplatin on day 1, 8, 15 (20 mg-30 mg/m(2)) in combination with octreotide 30 mg on day 1 plus imatinib 400 mg po daily. Primary outcome measure was the relative changes in plasma biomarkers over time.


RESULTS
Time-to-progression and overall survival was not different between the the two study trials. Within group 1-4, the mean relative increase from baseline to week 12 of treatment was 17, 18, 37, and 2% for s-E-selectin; -1, 90, 10, and -9% for VEGF-A; 18, 84, 141, and 74% for PDGF-BB, and 111, 142, 30, and 7% for serum AFP, respectively.


CONCLUSIONS
The increase of plasma levels for s-E-selectin and PDGF-BB seen in patients receiving chemotherapy alone may reflect activation of angiogenesis. In contrast, low-dose metronomic chemotherapy in combination with anti-angiogenic drugs seems to correlate with the least increase in biomarkers. Imatinib-octreotide temporarily leads to a decrease in PDGF-BB, whereas octreotide alone had no effect on PDGF-BB plasma levels.
Treiber
G
G
Department of Gastroenterology and Hepatology, University Hospital of Magdeburg, Magdeburg, Germany. gt@helico.de
Wex
T
T
Malfertheiner
P
P
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000188:drug therapy* / Q000517:prevention & control; D015282:Octreotide / Q000627:therapeutic use / Q000633:toxicity; D009944:Organoplatinum Compounds / Q000627:therapeutic use / Q000633:toxicity; D000077150:Oxaliplatin; D010879:Piperazines / Q000627:therapeutic use / Q000633:toxicity; D011743:Pyrimidines / Q000627:therapeutic use / Q000633:toxicity; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D010879:Piperazines; D011743:Pyrimidines; D000077150:Oxaliplatin; D000068877:Imatinib Mesylate; D015282:Octreotide