title: Prospective Evaluation of Sunitinib-Induced Cardiotoxicity in Patients with Metastatic Renal Cell Carcinoma.
abstract: Purpose:To prospectively evaluate cardiotoxicity risk with sunitinib in metastatic renal cell carcinoma (mRCC) routine clinical practice using comprehensive echocardiography and biomarker phenotyping.Experimental Design:In a multicenter prospective study of 90 patients with mRCC, echocardiography and biomarkers of cardiovascular injury and stress were quantified at baseline, 3.5, 15, and 33 weeks following sunitinib initiation. These "on-drug" visits corresponded to cycles 1, 3, and 6, respectively. Left ventricular (LV) dysfunction was defined as an absolute decline in LV ejection fraction (LVEF) by ≥10% to a value of <50%. Conditional survival analyses predicted the risk of LV dysfunction. Linear mixed-effects models estimated changes in LVEF, high-sensitivity Troponin I (hsTnI), and B-type natriuretic peptide (BNP) over time.Results:The predicted risk of LV dysfunction by cycle 6 was 9.7% (95% confidence interval, 3%-17%). The majority of events occurred in the first treatment cycle. This risk diminished to 5% and 2% in patients who had not experienced dysfunction by the completion of cycles 1 and 3, respectively. All evaluable patients who experienced LV dysfunction had subsequent improvement in LVEF with careful management. Six patients (6.7%) developed hsTnI elevations >21.5 pg/mL, and 11 additional patients (12.2%) developed BNP elevations >100 pg/mL. These elevations similarly tended to occur early and resolved over time.Conclusions:On average, patients with mRCC receiving sunitinib exhibit modest declines in LVEF and nonsignificant changes in hsTnI and BNP. However, approximately 9.7% to 18.9% of patients develop more substantive abnormalities. These changes occur early and are largely recoverable with careful management.Clin Cancer Res; 23(14); 3601-9. ©2017 AACR.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Vivek
authors.initials: V
authors.lastname: Narayan
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Stephen
authors.initials: S
authors.lastname: Keefe
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Naomi
authors.initials: N
authors.lastname: Haas
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Mary
authors.initials: M
authors.lastname: Putt
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Anna
authors.initials: A
authors.lastname: Catino
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: James
authors.initials: J
authors.lastname: Fang
authors.affiliation: Division of Oncology, Department of Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: Division of Cardiology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David
authors.initials: D
authors.lastname: Hyman
authors.affiliation: Division of Cardiology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Smith
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Finkelman
authors.affiliation: Division of Cardiology, Department of Pediatrics, The University of California, San Diego, La Jolla, California.
authors.forename: Hari K
authors.initials: HK
authors.lastname: Narayan
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, Madison, Wisconsin.
authors.forename: Steven
authors.initials: S
authors.lastname: Ewer
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Chantal
authors.initials: C
authors.lastname: ElAmm
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lenihan
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. bonnie.ky@uphs.upenn.edu.|Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.|Division of Cardiology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Ky
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D066126:Cardiotoxicity / Q000097:blood / Q000473:pathology*; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib; D019210:Troponin I / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000139:chemically induced / Q000473:pathology*
chemical_list: D007211:Indoles; D011758:Pyrroles; D019210:Troponin I; D020097:Natriuretic Peptide, Brain; D000077210:Sunitinib