Published in:
01-02-2009 | Original Paper
Impact of different anticancer regimens on biomarkers of angiogenesis in patients with advanced hepatocellular cancer
Published in: Journal of Cancer Research and Clinical Oncology | Issue 2/2009
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Objective
Advanced hepatocellular cancer (HCC) is a highly vascularised tumor with limited treament 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/m2), and group 4 with oxaliplatin on day 1, 8, 15 (20 mg–30 mg/m2) 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.