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Changes in VEGF-A-serum levels after DEBIRI-TACE in patients with liver metastases of chemorefractory colorectal cancer.

93 Background: TACE with irinotecan-loaded drug-eluting beads has shown activity in colorectal liver metastases. Among the factors potentially interfering with its effectiveness is a hypothetical neo-angiogenic reaction due to ischemia.


METHODS
Patients with predominant liver metastases from CRC which were refractory to chemotherapy and documented tumor progression during or shortly after the last chemotherapy, were prospectively treated with irinotecan-loaded drug-eluting beads with a size of 100-300 µm. Therapy was applied by a temporary catheter placed in the liver arteries. Usually each lobe of the liver was according to the recommended DEBIRI treatment algorithm. Each treatment of one liver lobe was performed with 1 vial of the 100-300 µm DC-Beads loaded with 100 mg irinotecan. Blood samples to measure the VEGF serum levels were taken before TACE and at days 7, 14, and 21 after first treatment.


RESULTS
Complete blood samples were taken from 15 patients from 2/11 to 2/12. 60% of patients had an increase of the VEGF-A-Level with a median of 107 %, 40% of patients had a decrease of the VEGF-A-Level with a median of - 39% respectively. The relative decrease of the VEGF-A-Levels depends on a prior liver resection (p=0.05), and a significant decrease was found in patients with a prior bevacizumab therapy (p=0.025). A trend to an increase in VEGF-A-Levels was detected in patients with a low count of liver metastases (p=0.087).


CONCLUSIONS
These findings show different behavior of the VEGF-A-levels after DEBIRI-TACE, suggesting that the occlusion of blood vessels and subsequent ischemia induces neo-angiogenesis due to these growth factors in a subset of 60% of the patients treated with a DEBIRI-TACE. We found a trend for a lower count of liver metastases, prior liver resection and a prior bevacizumab-therapy, respectively influencing the VEGF-A-Level-changes. The trend toward a decrease in patients with a prior bevacizumab therapy may be due to a neoangiogenesis-pathway other than VEGF-mediated. These first results could implicate that antiangiogenic drugs might be effective as an additive therapy to chemoembolization in a subset of patients, e.g., those with no prior bevacizumab therapy.