Impact of different anticancer regimens on biomarkers of angiogenesis in patients with advanced hepatocellular cancer.

objectiveAdvanced 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.

methodsTwo 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.

resultsTime-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.

conclusionsThe 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.