D-dimer elevation and paresis predict thromboembolic events during bevacizumab therapy for recurrent malignant glioma

Anticancer Res. 2013 May;33(5):2093-8.

Abstract

Background: The major side-effects of bevacizumab in glioma treatment are venous thromboembolic events (VTE). We retrospectively evaluated factors potentially predictive of thromboembolic events.

Patients and methods: Bevacizumab, alone or in combination with chemotherapy was used as salvage therapy for recurrence in malignant glioma every two weeks. None but one patient received anti-coagulants. Before each bevacizumab cycle differential blood cell count, kidney and liver parameters, D-dimers, neurological status, body-mass index, vital signs and signs of venous thrombosis were assessed.

Results: Thirty-eight patients received 428 cycles of bevacizumab. In five patients (13%), six VTE were observed. These complications were preceded four weeks before the onset of symptoms by D-dimer elevation above 0.865 mg/l [p<0.0001; sensitivity=89% (95% confidence interval=83-93%); specificity=89% (95% CI=52-100%)]. An existing hemiparesis constituted a 27-fold risk elevation for thrombotic complication (p<0.0001, χ(2)-test).

Conclusion: D-Dimer elevation or hemiparesis predict VTE under bevacizumab and chemotherapy, four weeks before the event becomes clinically apparent. Future investigations should determine if prophylactic anti-coagulants for patients at risk may reduce the risk of VTE.

Keywords: D-dimer; Recurrent malignant glioma; bevacizumab; deep venous thrombosis.

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / adverse effects
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Bevacizumab
  • Brain Neoplasms / drug therapy*
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism*
  • Follow-Up Studies
  • Glioma / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Staging
  • Paresis / chemically induced
  • Paresis / diagnosis*
  • Paresis / metabolism
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Thromboembolism / chemically induced
  • Thromboembolism / diagnosis*
  • Thromboembolism / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Bevacizumab