Circulating endothelial cells predict for response to bevacizumab-based chemotherapy in metastatic colorectal cancer

Cancer Chemother Pharmacol. 2011 Sep;68(3):763-8. doi: 10.1007/s00280-010-1543-2. Epub 2010 Dec 18.

Abstract

Purpose: Standardized enumeration of CEC counts is required to minimize variability and allow cross-studies comparisons. The purpose of this paper is to identify CEC threshold proposal, by CellSearch system, for determining response to bevacizumab-based chemotherapy in metastatic colorectal cancer.

Methods: From July 2007 to June 2008, 33 patients treated with FOLFOX4 plus bevacizumab were enrolled in a prospective study. From January 2007 to June 2007, before bevacizumab was approved by the government in Japan, 31 patients treated with FOLFOX4 as a control were enrolled. CECs of whole blood at the baseline, day 4, 2 weeks after initiation of chemotherapy were isolated and counted using CellSearch system.

Results: There was no correlation between CEC levels and the outcome in the FOLFOX4. In the bevacizumab-based chemotherapy, CEC levels at the baseline were significantly associated with the outcome. Patients with 65 or more CECs at the baseline had a shorter median PFS and OS, than the median PFS and OS of less than 65 CECs at the baseline in the bevacizumab-based chemotherapy (P = 0.003, P = 0.027, respectively). By univariate and multivariate Cox proportional-hazards regression, CEC levels (cut-off; 65) at the baseline indicated the strongest predictor for the outcome to bevacizumab-based chemotherapy.

Conclusion: A threshold of lower than 65 CECs, by the CellSearch System, at the baseline was a significant predictor of the outcome for colorectal cancer patients treated with bevacizumab-based chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Cell Count
  • Cell Separation
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Endothelial Cells / physiology*
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Kaplan-Meier Estimate
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis / pathology
  • Organoplatinum Compounds / therapeutic use
  • Predictive Value of Tests
  • Prospective Studies
  • Regression Analysis
  • Survival Analysis
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Organoplatinum Compounds
  • Bevacizumab
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol