title: Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell Carcinoma Patients without Overt Metastases: Results from ASSURE, ECOG 2805.
abstract: OBJECTIVE
  Sunitinib and sorafenib are used widely in the treatment of renal cell carcinoma (RCC). These agents are associated with a significant incidence of cardiovascular (CV) dysfunction and left ventricular ejection fraction (LVEF) declines, observed largely in the metastatic setting. However, in the adjuvant population, the CV effects of these agents remain unknown. We prospectively defined the incidence of cardiotoxicity among resected, high-risk RCC patients treated with these agents.
  
  
  METHODS
  Sunitinib, sorafenib, or placebo was administered for up to 12 months in patients with high-risk, resected RCC. LVEF was measured by multigated acquisition (MUGA) scans at standard intervals. Additional CV adverse events were reported according to NCI Common Terminology Criteria for Adverse Events (CTCAE).
  
  
  RESULTS
  Among 1,943 patients randomized, 1,599 had at least 1 post-baseline MUGA. Within 6 months, 21 patients (1.3%) experienced a cardiac event, defined as an LVEF decline from baseline that was >15% and below the institutional lower limit of normal. Nine of 513 patients (1.8%) were on sunitinib, 7 of 508 (1.4%) on sorafenib, and 5 of 578 (0.9%) on placebo (P = 0.28 and 0.56 comparing sunitinib and sorafenib to placebo, respectively). With dose interruption or adjustment, 16 of the 21 recovered their LVEF to >50%. The incidence of symptomatic heart failure, arrhythmia, or myocardial ischemia did not differ among groups.
  
  
  CONCLUSIONS
  In the adjuvant setting, we prospectively define low incidence of cardiotoxicity with sunitinib and sorafenib. These findings may be related to close CV monitoring, or potentially to fewer CV comorbidities in our nonmetastatic population.
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania. Naomi.haas@uphs.upenn.edu.
authors.forename: Naomi B
authors.initials: NB
authors.lastname: Haas
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Judith
authors.initials: J
authors.lastname: Manola
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Ky
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Uzzo
authors.affiliation: University of California at San Diego, San Diego, California.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kane
authors.affiliation: University of Toronto, Toronto, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Jewett
authors.affiliation: Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Lori
authors.initials: L
authors.lastname: Wood
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.affiliation: Beth Israel Deaconess Hospital, Boston, Massacheusetts.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.affiliation: Our Lady of Mercy Cancer Center, New York Medical College, Bronx, New York.
authors.forename: Janice J
authors.initials: JJ
authors.lastname: Dutcher
authors.affiliation: Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin.
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
authors.forename: Robert S
authors.initials: RS
authors.lastname: DiPaola
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D000077157:Sorafenib; D000077210:Sunitinib; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib