title: Contemporary trends in high-dose interleukin-2 use for metastatic renal cell carcinoma in the United States.
abstract: BACKGROUND
  Targeted therapies (TTs) have revolutionized metastatic renal cell carcinoma (mRCC) treatment in the past decade, largely replacing immunotherapy including high-dose interleukin-2 (HD IL-2) therapy. We evaluated trends in HD IL-2 use for mRCC in the TT era.
  
  
  METHODS
  Our cohort comprised a weighted estimate of all patients undergoing HD IL-2 treatment for mRCC from 2004 to 2012 using the Premier Hospital Database. We assessed temporal trends in HD IL-2 use including patient, disease, and hospital characteristics stratified by era (pre-TT uptake: 2004-2006, uptake: 2007-2009, and post-TT uptake: 2010-2012) and fitted multivariable regression models to identify predictors of treatment toxicity and tolerability.
  
  
  RESULTS
  An estimated 2,351 patients received HD IL-2 therapy for mRCC in the United States from 2004 to 2012. The use decreased from 2004 to 2008. HD IL-2 therapy became increasingly centralized in teaching hospitals (24% of treatments in 2004 and 89.5% in 2012). Most patients who received HD IL-2 therapy were men, white, younger than 60 years, had lung metastases, and were otherwise healthy. Vasopressors, intensive care unit admission, and hemodialysis were necessary in 53.4%, 33.0%, and 7.1%, respectively. Factors associated with toxicities in multivariable analyses included being unmarried, male sex, and multiple metastatic sites. African Americans and patients with single-site metastases were less likely to receive multiple treatment cycles.
  
  
  CONCLUSIONS
  HD IL-2 therapy is used infrequently for mRCC in the United States, and its application has diminished with the uptake of TT. Patients are being increasingly treated in teaching hospitals, suggesting a centralization of care and possible barriers to access. A recent slight increase in HD IL-2 therapy use likely reflects recognition of the inability of TT to effect a complete response.
authors.affiliation: Division of Urology, Brigham and Women׳s Hospital, Harvard Medical School, Boston, MA; Department of Urology, Massachusetts General Hospital, Boston, MA. Electronic address: Callard@mgh.harvard.edu.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Allard
authors.affiliation: Division of Urology, Brigham and Women׳s Hospital, Harvard Medical School, Boston, MA; Department of Urology, Massachusetts General Hospital, Boston, MA.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gelpi-Hammerschmidt
authors.affiliation: Kidney Cancer Center, Dana-Farber Cancer Institute, Brigham and Women׳s Hospital, Harvard Medical School, Boston, MA.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Harshman
authors.affiliation: Kidney Cancer Center, Dana-Farber Cancer Institute, Brigham and Women׳s Hospital, Harvard Medical School, Boston, MA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Section of Urologic Oncology, Rutgers Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ.
authors.forename: Izak
authors.initials: I
authors.lastname: Faiena
authors.affiliation: Section of Urologic Oncology, Rutgers Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ.
authors.forename: Parth
authors.initials: P
authors.lastname: Modi
authors.affiliation: Department of Urology, Stanford School of Medicine, Palo Alto, CA.
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Chung
authors.affiliation: Division of Urology, Brigham and Women׳s Hospital, Harvard Medical School, Boston, MA; Department of Urology, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: Ilker
authors.initials: I
authors.lastname: Tinay
authors.affiliation: Section of Urologic Oncology, Rutgers Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, NJ.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Singer
authors.affiliation: Division of Urology, Brigham and Women׳s Hospital, Harvard Medical School, Boston, MA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Chang
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D014481:United States
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2
keywords: High-dose interleukin-2; Immunotherapy; Kidney cancer; Renal cell carcinoma; Therapy trends; Toxicity