Abstract
3555 Background: Anti-angiogenic therapy has demonstrated efficacy in the treatment of metastatic renal cell carcinoma (MRCC). New surrogate biomarkers are needed to optimize the potential of this novel therapy. Circulating endothelial cell (CEC) and progenitor cell (CEP) measurement has been proposed to monitor anti-angiogenic drug activity and treatment efficiency. Methods: 21 patients (pts) with MRCC were analysed. Among them, 16 were monitored both at baseline and 2 -3 weeks after start of anti-angiogenic treatment (14 pts received sutinimib and 2, nexavar). CECs were measured in one ml erythocyte lysed whole blood by four color flow cytometry (FCM) and identified by a CD45-CD31+CD146+ 7-amino-actinomycin (7AAD)- phenotype. Enumeration of CEC was validated by spiking whole blood with human umbilical vein cells and by immunohistochemical staining of the cell sorted fraction with endothelial markers (Ulex-Europaeus-lectin-1 and Von Willebrand factor). Median CEC value in 20 healthy subjects was 5.5 /ml (range 0–15) wheras this value was 16/ml (range 0–179) in 80 metastatic cancer patients. CEPs were measured by FCM as extremely rare events with a CD45dimCD34+ VEGFR2+7AAD- phenotype. Results: Median MRCC baseline CEC value was 17/ml (range 3 to 101). 16 pts had CEC levels that were two-fold greater than healthy subjects (>10/ml). Preliminary data showed a dramatic drop in CEC levels in patients that responded to therapy. Median baseline CEP value was 0.49% of hematopoietic stem cells (HSC), with ranges from 0.06% to 9% (absolute counts: 10/ml range 1 to 181/ml). Eight patients had CEP values greater than 1% of HSC and all had high tumor burden. Among the 16 pts monitored, all except 2 showed a dramatic increase in CEPs after treatment suggesting that anti-VEGFR2 targeted therapy might induce peripheral accumulation of CEP. Updated data and correlations with prognostic factors and clinical outcome will be presented. Conclusion: During anti-angiogenic therapy, dramatic changes in both CEC and CEP levels were observed. Predictive values of CEC and CEP are currently under evaluation. No significant financial relationships to disclose.
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