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

Abstract

BACKGROUND:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

TRIAL REGISTERY:

clinicaltrialsregister.eu EudraCT 2007-003705-27.

• Authors: Thorsten Fuereder, Volker Wacheck, Sabine Strommer, Peter Horak, Marion Gerschpacher, Wolfgang Lamm, Danijel Kivaranovic, Michael Krainer
• Journal: PloS one (PLoS One) Vol. 9 Issue 4 Pg. e95310 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24755958 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Taxoids
• Docetaxel
• Prostate-Specific Antigen

Topics

• Aged
• Biomarkers, Tumor (metabolism)
• Bone and Bones (diagnostic imaging, drug effects, pathology)
• Cell Movement (drug effects)
• Disease-Free Survival
• Docetaxel
• Endothelial Progenitor Cells (drug effects, pathology)
• Humans
• Kinetics
• Male
• Middle Aged
• Prostate-Specific Antigen (metabolism)
• Prostatic Neoplasms, Castration-Resistant (diagnostic imaging, drug therapy, pathology)
• Radiography
• Taxoids (pharmacology, therapeutic use)