Circulating endothelial progenitors and CXCR4-positive circulating endothelial cells are predictive markers for bevacizumab

Authors

  • Satoshi Matsusaka MD, PhD,

    1. Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
    Search for more papers by this author
  • Yuji Mishima PhD,

    1. Cancer Chemotherapy Center, Clinical Chemotherapy, Japanese Foundation for Cancer Research, Tokyo, Japan
    Search for more papers by this author
  • Mitsukuni Suenaga MD, PhD,

    1. Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
    Search for more papers by this author
  • Yasuhito Terui MD, PhD,

    1. Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
    Search for more papers by this author
  • Ryoko Kuniyoshi PhD,

    1. Cancer Chemotherapy Center, Clinical Chemotherapy, Japanese Foundation for Cancer Research, Tokyo, Japan
    Search for more papers by this author
  • Nobuyuki Mizunuma MD, PhD,

    1. Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
    Search for more papers by this author
  • Kiyohiko Hatake MD, PhD

    Corresponding author
    1. Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
    • Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan
    Search for more papers by this author
    • Fax: (011) 81-3-3570-0343


  • The excellent technical assistance of Harumi Shibata and Mariko Mikuniya is greatly appreciated.

Abstract

BACKGROUND:

Bevacizumab plus chemotherapy is a standard option in the treatment of metastatic colorectal cancer (mCRC). The aim of this study was to investigate the potential of circulating endothelial cell progenitors (CEPs) and phenotypical circulating endothelial cells (CECs) as surrogate markers of clinical outcome in mCRC patients to identify responders to bevacizumab in combination with chemotherapy.

METHODS:

A total of 69 patients with measurable mCRC were enrolled in this prospective study. Whole blood samples were analyzed before initiation of treatment and on days 4 and 14. Phenotypical CECs and CEPs were then isolated and enumerated by using flow cytometry.

RESULTS:

CEP levels of less than 0.04% on day 4 were significantly associated with longer progression-free survival (PFS) and overall survival (OS) (P < .001, P = .002, respectively) as compared with levels of 0.04% or more. In addition, CXCR4-positive CEC levels of less than 20% at baseline were significantly associated with longer PFS and OS as compared other indicators investigated (P < .001, P = .002, respectively).

CONCLUSIONS:

Levels of CEPs on day 4 and proportion of CXCR4-positive CECs at baseline were correlated with the prognosis of bevacizumab combination chemotherapy, suggesting that these surrogate markers may play a core role in the selection of candidates for bevacizumab treatment. Cancer 2011;. © 2011 American Cancer Society.

Ancillary