title: The high incidence of vascular thromboembolic events in patients with metastatic or unresectable urothelial cancer treated with platinum chemotherapy agents.
abstract: BACKGROUND
  The current study compared the incidence of vascular thromboembolic events (VTEs) in patients with metastatic or unresectable urothelial carcinoma (UC) who were treated with gemcitabine and carboplatin (GCb); gemcitabine, carboplatin, and bevacizumab (GCbBev); or gemcitabine and cisplatin (GCis).
  
  
  METHODS
  Patients with UC who were treated with GCbBev on protocol were analyzed prospectively and 2 contemporary control cohorts receiving GCb or GCis were evaluated retrospectively. VTE was defined as either venous or arterial (myocardial infarctions or cerebral vascular accidents) thrombosis. VTEs were considered to be related to treatment if they occurred during treatment or within 4 weeks of the completion of treatment. Associations with chemotherapy regimen were tested using either the Fisher exact test or Kruskal-Wallis test. Clinical factors associated with VTEs were analyzed using conditional logistic regression stratified by treatment regimen.
  
  
  RESULTS
  Among 198 patients, VTEs occurred in 13 of 51 patients treated with GCbBev (26%), 22 of 92 patients treated with GCb (24%), and 8 of 55 patients treated with GCis (15%). Patient characteristics were significantly different between the treatment cohorts in terms of age, prior cystectomy, tumor location near pelvic vessels, Khorana risk group, and receipt of antiplatelet therapy. The incidence of VTE and type of VTE (arterial vs venous) did not differ by type of chemotherapy. Prior cystectomy was associated with an increased risk of VTE (odds ratio, 2.2; 95% confidence interval, 1.0-4.9 [P = .047]).
  
  
  CONCLUSIONS
  The incidence of VTE in Cis-treated patients was similar to prior reports. However, the VTE rate in Cb-treated patients was > 20%, a figure not previously defined in patients with UC and higher than expected. This high incidence of both Cis-related and Cb-related VTEs warrants greater awareness by treating physicians and deserves further study. Cancer 2016;122:712-721. © 2015 American Cancer Society.
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Tully
authors.affiliation: Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Apolo
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Zabor
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Regazzi
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Irina
authors.initials: I
authors.lastname: Ostrovnaya
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Helena F
authors.initials: HF
authors.lastname: Furberg
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Rosenberg
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Bajorin
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D016022:Case-Control Studies; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D007682:Kidney Pelvis / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D011446:Prospective Studies; D012189:Retrospective Studies; D020521:Stroke / Q000453:epidemiology*; D014516:Ureteral Neoplasms / Q000188:drug therapy / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D054556:Venous Thromboembolism / Q000453:epidemiology*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000068258:Bevacizumab; D016190:Carboplatin; D002945:Cisplatin; D000093542:Gemcitabine
keywords: bladder cancer; carboplatin; cisplatin; thrombosis; urothelial carcinoma