HOME HELP FEEDBACK HOW TO CITE ABSTRACTS ARCHIVE CME INFORMATION SEARCH Cancer Research Clinical Cancer Research Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics Molecular Cancer Research Cancer Prevention Research Cancer Prevention Journals Portal Cancer Reviews Online Annual Meeting Education Book Meeting Abstracts Online		QUICK SEARCH:   [advanced] Author: Keyword(s):

Services Similar articles in this journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by McKeegan, E. M. Articles by Lesniewski, R. Search for Related Content PubMed Articles by McKeegan, E. M. Articles by Lesniewski, R.

Proffered Abstract (Plenary Session): Monitoring Response During Cancer Therapy

Characterization of human circulating endothelial cells to monitor response to antitumor therapy in human clinical trials

Abbott Laboratories, Abbott Park, IL

Abstract

PR-5

Circulating endothelial cells (CEC) have been observed at elevated concentrations in preclinical models of cancer and in cancer patients. Modulations of the CEC concentrations have been correlated with responses to therapy in preclinical and clinical settings (1, 2). Flow cytometric methods to enumerate CEC and to examine these cells phenotypically for activation status (CD106), stage of differentiation (CD133) and apoptotic status (Annexin V) were established for use in human cancer patients. CEC were evaluated in humans, both healthy volunteers and patients enrolled in Abbott Oncology clinical trials. Examination of CEC in 84 healthy humans demonstrated a low and consistent CEC number averaging 5.3 0.3 CEC/µl. In 61 patients with soft tissue sarcoma and 75 patients with renal cell carcinoma enrolled in clinical trials with the anti-angiogenic thrombospondin-1 mimetic peptide, ABT-510, baseline CEC averaged 10.5 +/- 1.5 CEC/µl (p< 0.0004) and 16.2+/-1.8 CEC/µl (p< 0.0001), respectively. Analysis of baseline CEC concentrations using a predictive cut-off of 15 CEC/µl stratified the patients for time to progression in these two studies. In the sarcoma study, patients with CEC > 15 had a median time to progression of 2 months, compared to 3 months for patients with CEC < 15 (p<0.0022). Similarly, in the renal cell study, median time to progression was 2 months, compared to 5 months for patients with CEC < 15 (p<0.0001). Additionally, in the renal cancer study, CEC concentration at baseline remained predictive of outcome in patients even following segregation into favorable (p<0.03) and intermediate risk groups (p< 0.008), by the Memorial Sloan Kettering Cancer Center (MSKCC) risk criteria. CEC concentrations are significantly higher in humans and animals with cancer. Baseline CEC may function as a predictive marker for outcome, however the relationship to ABT-510 therapy has not been established. Further evaluation of this marker as a general prognostic marker or as an independent risk variable for ABT-510 and other anti-angiogenic therapies is warranted. 1. Mancuso P, B.A., Pruneri G, et al., Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood, 2001. 97: p. 3658-3661.2. Monestiroli S, M.P., Burlini A, et al., Kinetics and viability of circulating endothelial cells as surrogate angiogenesis marker in an animal model of human lymphoma. Can Res, 2001. 61: p. 4341-4344.