Background

New surrogate biomarkers such as circulating endothelial cell (CEC) and progenitor cell (CEP) have been proposed to monitor anti-vascular drug activity. During anti-angiogenic therapy, dramatic changes in both CEC and CEP levels were observed. Moreover, these biomarkers may also be used as a candidate prognostic and predictive biomarker in patients with advanced cancer.

Methods

Medical charts of patients treated in one centre and enrolled into five Phase I trials with anti-vascular therapies between October 2005 and April 2009 were reviewed for clinical characteristics and validated clinical prognostic factors (albumin, lactate dehydrogenase, number of metastatic sites)(Arkenau et al, JCO 2009).

Overall 70 patients had CEC or CEP evaluation at baseline. 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… CEPs were measured in 10ml blood after progenitor cell enrichment and were identified by FCM as extremely rare events with a CD45dimCD34+VEGFR2+7AAD- phenotype.

We studied the impact of CEC and CEP values on the overall survival (OS) adjusted on the clinical prognostic score.

Results

The median age was 50 years (range, 21 to 78 years).

Median baseline CEC value was 12/ml (range, 0 to 154).

The CEPs were measured in 57 patients; the median CEP value was 1.3% of hematopoietic stem cells, with range from 0% to 32.5% (absolute counts: 12/ml, range, 0 to 392/ml). 31/57 had CEP values greater than 1% of HSC.

Median follow-up was 23 months. The risk of death was significantly increased in patients with prognostic score greater than 0 as compared to patients with score equal to 0 (Median OS 9.2 versus 24.2 respectively) as well as in patients with increased CEP (>1%) as compared to those with lower values (Median OS 9.0 versus 13.3). Both factors remained significant in multivariate analysis (HR=3.9, 95%CI, 0.95-16.6, p=0.02 and HR=2.1, 95%CI, 1.0-4.3, p=0.04, respectively). We did not observe any relationship between the CEC level and the outcome.

Conclusion

This analysis suggests that a prognostic score based on CEP level combined with clinical characteristics could be a helpful tool to determine the prognosis of patients with advanced cancers enrolled into phase 1 trials. Further studies are requested to confirm these findings.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 852.