Circulating endothelial progenitor cells in castration resistant prostate cancer: a randomized, controlled, biomarker study

• Published in: PloS one Vol. 9; no. 4; p. e95310
• Main Authors: Fuereder, Thorsten, Wacheck, Volker, Strommer, Sabine, Horak, Peter, Gerschpacher, Marion, Lamm, Wolfgang, Kivaranovic, Danijel, Krainer, Michael
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2014; Public Library of Science (PLoS)
• Subjects: Aged; Analysis; Angiogenesis; Biomarkers; Biomarkers, Tumor - metabolism; Bone and Bones - diagnostic imaging; Bone and Bones - drug effects; Bone and Bones - pathology; Bone marrow; Cancer; Cancer cells; Cancer therapies; Castration; Cell Movement - drug effects; Cells (biology); Chemotherapy; Clinical trials; Disease-Free Survival; Docetaxel; Drug dosages; Endothelial cells; Endothelial Progenitor Cells - drug effects; Endothelial Progenitor Cells - pathology; Endothelium; Humans; Internal medicine; Kinetics; Male; Medicine; Medicine and Health Sciences; Metastasis; Middle Aged; Molecular modelling; Oncology, Experimental; Patients; Pediatrics; Pharmacodynamics; Pharmacology; Prostate cancer; Prostate-Specific Antigen - metabolism; Prostatic Neoplasms, Castration-Resistant - diagnostic imaging; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - pathology; Radiography; Risk factors; Stem cells; Studies; Taxoids - pharmacology; Taxoids - therapeutic use; Therapy; Toxicity; Tumors; Austria
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0095310

Endothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC) patients. Chemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d), in combination with docetaxel (75 mg/m2) or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy. A total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable) counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001). However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30%) patients responded to therapy with a 50% PSA decline, while 9 (64%) patients showed a PSA decline in the combination group (n.s.). The median PFS in the docetaxel monotherapy group was 3.1 months (2.6-3.6 months, 95% CI) and 6.2 months (4.9-7.4 months, 95% CI; p = 0.062) in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable. In summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However, docetaxel/sunitinib therapy resulted in a better response in terms of PSA decline and a trend towards improved PFS. clinicaltrialsregister.eu EudraCT 2007-003705-27.