title: Routine proteinuria monitoring for bevacizumab in patients with gynecologic malignancies.
abstract: BACKGROUND
  Proteinuria leading to nephrotic syndrome is a rare adverse event arising from treatment with bevacizumab. There is limited evidence to guide the frequency and appropriate test for monitoring for proteinuria. The purpose of this study was to determine the prevalence and severity of proteinuria during bevacizumab administration to patients with gynecologic malignancies, and to evaluate risk factors associated with this toxicity; a secondary objective was to evaluate the cost of routine proteinuria monitoring to assess for opportunities of cost containment that could change clinical practice.
  
  
  METHODS
  A retrospective chart review was performed at an academic gynecologic oncology clinic. Women over 18 years of age with a diagnosed gynecologic malignancy were evaluated for the development of proteinuria while receiving bevacizumab treatment as measured by a urine protein-to-creatinine ratio. Patient and disease-specific risk factors were evaluated using logistic regression to determine correlations of risk factors to development of proteinuria. Cost assessment was performed using institution-specific data for urine laboratory tests.
  
  
  RESULTS
  Eighty-nine patients were identified, and the overall prevalence of proteinuria of any grade was 35%. The mean number of bevacizumab cycles was 13 (2-64 cycles). The majority of patients experienced grade 1 proteinuria (70%, 62 patients). Grade 3 proteinuria was observed in two patients (2%). There was a trend toward increased bevacizumab cycles associated with increased grade proteinuria (p = 0.053), however there were no factors significantly associated with the development of proteinuria as measured by urine protein-to-creatinine ratio.
  
  
  CONCLUSIONS
  Monitoring of urine protein-to-creatinine ratios with each cycle may be unnecessary due to the low prevalence of grade 3 proteinuria observed. Additionally, urine protein-to-creatinine ratios may not provide adequate assessment of proteinuria toxicity associated with bevacizumab therapy. Potential cost savings opportunities for the institution can be realized with a cost-reductive monitoring algorithm that will utilize less costly laboratory techniques for patients at high risk of developing proteinuria.
authors.affiliation: Department of Pharmacy, University of Washington Medical Center, Seattle, WA, USA cathlee@seattlecca.org.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, University of Washington Medical Center, Seattle, WA, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Alwan
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Sun
authors.affiliation: Division of Gynecologic Oncology, University of Washington Medical Center, Seattle, WA, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: McLean
authors.affiliation: Division of Gynecologic Oncology, University of Washington Medical Center, Seattle, WA, USA.
authors.forename: Renata R
authors.initials: RR
authors.lastname: Urban
mesh_terms: D000328:Adult; D000368:Aged; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects*; D000068258:Bevacizumab / Q000009:adverse effects*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005833:Genital Neoplasms, Female / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology; D011507:Proteinuria / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D016482:Urinalysis / Q000379:methods
chemical_list: D000074322:Antineoplastic Agents, Immunological; D000068258:Bevacizumab
keywords: Bevacizumab; gynecology oncology; proteinuria; urine protein-to-creatinine ratio; vascular endothelial growth factor