title: Fatigue with vascular endothelial growth factor receptor tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors in patients with renal cell carcinoma (RCC) and other malignancies: A meta-analysis of randomized clinical trials.
abstract: A trial-level meta-analysis of randomized phase II/III controlled trials in renal cell carcinoma (RCC) and other malignancies was conducted to systematically determine the relative risk (RR) of fatigue, a common side effect associated with single agent therapy with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) and mammalian target of rapamycin inhibitors (mTORi). The RR of all grade fatigue and high grade fatigue in 7304 patients from 19 trials was 1.35 (95% CI 1.22-1.49, p<0.001) and 1.33 (95% CI 0.97-1.82, p=0.08), respectively in patients receiving VEGFR TKIs or mTORi. The summary incidence of all grade and high grade fatigue in the drug arm was 38.2% (95% CI 31.8-45.1) and 4.0% (95% CI 2.8-5.7), respectively. The type of drug (VEGFR TKI vs. mTORi), line of therapy, age, type of tumor (RCC vs. others) and median duration of therapy did not affect the risk of all-grade fatigue.
authors.affiliation: Department of Internal Medicine, University of Alabama at Birmingham (UAB), AL, United States.
authors.forename: Pooja
authors.initials: P
authors.lastname: Ghatalia
authors.affiliation: Department of Food and Nutrition, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Youjin
authors.initials: Y
authors.lastname: Je
authors.affiliation: Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Nguyen
authors.affiliation: Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States.
authors.forename: Quoc-Dien
authors.initials: QD
authors.lastname: Trinh
authors.affiliation: Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, United States. Electronic address: toni_choueiri@dfci.harvard.edu.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Department of Internal Medicine, Section of Medical Oncology, UAB Medical Center, United States. Electronic address: gsonpavde@uabmc.edu.
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D058570:TOR Serine-Threonine Kinases
keywords: Fatigue; Mammalian target of rapamycin inhibitors; Meta-analysis; Tyrosine kinase inhibitors; Vascular endothelial growth factor receptor