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Circulating D-dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma.

Publication ,  Journal Article
Blackwell, K; Hurwitz, H; Liebérman, G; Novotny, W; Snyder, S; Dewhirst, M; Greenberg, C
Published in: Cancer
July 1, 2004

BACKGROUND: Fibrin formation is required for tumor angiogenesis, metastasis, and invasion. D-dimer, a fibrin degradation product, is produced when crosslinked fibrin is degraded by plasmin. The current study prospectively examined D-dimer levels in patients with metastatic colorectal carcinoma treated in a Phase II randomized trial comparing bevacizumab (Avastin, Genentech, South San Francisco, CA) plus 5-fluorouracil/leucovorin (5-FU/LV) with 5-FU/LV alone. METHODS: At least one circulating D-dimer level was evaluable in 98 of the 104 previously untreated patients with metastatic colorectal carcinoma in the current trial. Plasma D-dimer levels were determined using a quantitative immunoassay kit at enrollment, before each treatment, and at the time of trial completion or disease progression. RESULTS: At trial enrollment, 86 of 104 patients (88%) had elevated D-dimer levels (> 20 ng/mL), and 86 of 102 patients (84%) had elevated carcinoembryonic antigen (CEA) levels (> 3 ng/mL). Baseline D-dimer levels were correlated with the following baseline characteristics: CEA (Pearson coefficient, 0.31; P = 0.002), albumin levels (Pearson coefficient, -0.32; P = 0.002), tumor burden (Pearson coefficient, 0.30; P = 0.003), and number of metastatic sites (Pearson coefficient, 0.21; P = 0.04). At the time of progression, plasma D-dimer levels reached a maximum postbaseline value in 51 of 61 patients (84%), whereas the CEA level was at its maximum postbaseline value in 39 of 55 patients (71%). Baseline D-dimer levels were a strong predictor of overall survival on univariate analysis (P = 0.008) and multivariate analysis (P = 0.03). Overall, treatment with bevacizumab (5 mg/kg) and baseline D-dimer levels were the only predictors of overall survival (P < 0.05). CONCLUSIONS: The current study indicates that fibrin remodeling is an important prognostic feature in metastatic colorectal carcinoma. D-dimer levels should be incorporated into prognostic models, and D-dimer may represent a useful biomarker for patients treated with antiangiogenic agents.

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Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

July 1, 2004

Volume

101

Issue

1

Start / End Page

77 / 82

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Leucovorin
  • Humans
  • Fluorouracil
  • Fibrin Fibrinogen Degradation Products
  • Female
  • Disease Progression
  • Colorectal Neoplasms
 

Citation

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Blackwell, K., Hurwitz, H., Liebérman, G., Novotny, W., Snyder, S., Dewhirst, M., & Greenberg, C. (2004). Circulating D-dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma. Cancer, 101(1), 77–82. https://doi.org/10.1002/cncr.20336
Blackwell, Kimberly, Herbert Hurwitz, Grazyna Liebérman, William Novotny, Stacey Snyder, Mark Dewhirst, and Charles Greenberg. “Circulating D-dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma.Cancer 101, no. 1 (July 1, 2004): 77–82. https://doi.org/10.1002/cncr.20336.
Journal cover image

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

July 1, 2004

Volume

101

Issue

1

Start / End Page

77 / 82

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Leucovorin
  • Humans
  • Fluorouracil
  • Fibrin Fibrinogen Degradation Products
  • Female
  • Disease Progression
  • Colorectal Neoplasms