Therapeutic significance of a D-dimer cut-off level of >3 µg/ml in colorectal cancer patients treated with standard chemotherapy plus bevacizumab

Jpn J Clin Oncol. 2010 Oct;40(10):933-7. doi: 10.1093/jjco/hyq058. Epub 2010 May 21.

Abstract

Objective: The risk of venous thromboembolism has been reported to increase when receiving bevacizumab. Many cancer patients are reported to have elevated D-dimer levels. It is not clear what D-dimer level might indicate an increased risk of venous thromboembolism in the colorectal cancer patients treated with bevacizumab-containing chemotherapy.

Methods: The D-dimer levels and any event concurrent with an elevated D-dimer level were evaluated in patients receiving bevacizumab. The D-dimer cut-off level was determined using the receiver-operating characteristic analysis. The selection criteria were as follows: histologically proven metastatic and unresectable colorectal adenocarcinoma; no prior chemotherapy containing bevacizumab; D-dimer test performed repetitively on the baseline and during bevacizumab administration; no venous thromboembolism identified at the baseline; and enhanced computed tomographic scan performed every 2 months.

Results: Sixty-nine patients were included. The chemotherapy regimens with bevacizumab included the regimen of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), the regimen of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), and leucovorin-modulated 5-fluorouracil. The median baseline D-dimer level was 1.2 µg/ml. The appropriate D-dimer cut-off level was 3 µg/ml with the negative predictive value of 98% and relative risk of 6.9. Twenty-one of 69 patients showed elevated D-dimer levels of >3 µg/ml, with 11 patients for unknown reasons, 6 with tumor progression, 3 with venous thromboembolism and 1 with sepsis. In the remaining 48 patients whose D-dimer levels were ≤3 µg/ml, only one patient developed a venous thromboembolism.

Conclusions: A D-dimer cut-off level of 3 µg/ml might be a useful indicator level to exclude venous thromboembolism or show an increased risk for venous thromboembolism in colorectal cancer patients treated with bevacizumab-containing chemotherapy.

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis*
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use
  • Retrospective Studies
  • Sensitivity and Specificity
  • Sepsis / blood
  • Sepsis / chemically induced
  • Sepsis / diagnosis
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / chemically induced
  • Venous Thromboembolism / diagnosis

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Fibrin Fibrinogen Degradation Products
  • Organoplatinum Compounds
  • fibrin fragment D
  • Bevacizumab
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • Folfox protocol
  • IFL protocol