title: Therapeutic significance of a D-dimer cut-off level of >3 µg/ml in colorectal cancer patients treated with standard chemotherapy plus bevacizumab.
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.
authors.affiliation: Division of Digestive Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577 Japan. satoshi-jp@umin.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mochizuki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshino
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fuse
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikematsu
authors.forename: Keiko
authors.initials: K
authors.lastname: Minashi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yano
authors.forename: Makoto
authors.initials: M
authors.lastname: Tahara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kaneko
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Doi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis; D054556:Venous Thromboembolism / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005338:Fibrin Fibrinogen Degradation Products; D009944:Organoplatinum Compounds; C036309:fibrin fragment D; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin