title: Thromboembolic events in patients with colorectal cancer receiving the combination of bevacizumab-based chemotherapy and erythropoietin stimulating agents.
abstract: OBJECTIVE
  To investigate whether the incidence of thromboembolic events (venous and arterial) increases when bevacizumab-based chemotherapy and erythropoietin stimulating agents (ESAs) are used in combination versus alone.
  
  
  METHODS
  A retrospective, pilot study of 79 colorectal cancer patients treated with chemotherapy were divided into 3 groups: bevacizumab (n = 28), ESA (n = 21), and bevacizumab plus ESA (n = 28). The primary end point was the incidence of thromboembolic events. Secondary endpoints included median time-to-event; effect of anticoagulation; and association with concurrent chemotherapy, baseline risk factors, hemoglobin, and performance status.
  
  
  RESULTS
  The incidence of thromboembolic events was 11% in the bevacizumab group, 23.8% in the ESA group, and 30% in the combination group (P = 0.194). The median time-to-event was 7.5, 3.5, and 2.5 months, respectively (P = 0.060). The 5 month difference in time-to-event between the bevacizumab group and combination group was significant (P = 0.045). When combining all patients, ESA treatment, prior venous thromboembolic event (VTE), obesity, cardiac disease, and use of exogenous hormones were strong predictors for thromboembolic events. Prior VTE was a strong predictor in those patients in the combination group.
  
  
  CONCLUSIONS
  The incidence of thromboembolic events was increased with the combination of bevacizumab plus ESA compared with either agent alone with chemotherapy. Median time-to-event in the combination group was significantly shorter compared with the bevacizumab group. Prior VTE, cardiac disease, obesity, and exogenous hormone use should be taken in consideration when using the combination of bevacizumab and ESAs.
authors: Department of Pharmacy Services, The University Hospital, University of Cincinnati, Cincinnati, Ohio, USA. julianna.roddy@gmail.com
authors: Julianna V F
authors: JV
authors: Roddy
authors: Suzanne M
authors: SM
authors: Partridge
authors: Michelle L
authors: ML
authors: Rockey
authors: Jane M
authors: JM
authors: Pruemer
authors: Jeff J
authors: JJ
authors: Guo
authors: Shaili J
authors: SJ
authors: Desai
authors: Malek M
authors: MM
authors: Safa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D011994:Recombinant Proteins; D012189:Retrospective Studies; D015996:Survival Rate; D013923:Thromboembolism / Q000139:chemically induced*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006454:Hemoglobins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D000068258:Bevacizumab