title: Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis.
abstract: OBJECTIVE
  Cancer-related fatigue (CRF) remains one of the most prevalent and troublesome adverse events experienced by patients with cancer during and after therapy.
  
  
  OBJECTIVE
  To perform a meta-analysis to establish and compare the mean weighted effect sizes (WESs) of the 4 most commonly recommended treatments for CRF-exercise, psychological, combined exercise and psychological, and pharmaceutical-and to identify independent variables associated with treatment effectiveness.
  
  
  METHODS
  PubMed, PsycINFO, CINAHL, EMBASE, and the Cochrane Library were searched from the inception of each database to May 31, 2016.
  
  
  METHODS
  Randomized clinical trials in adults with cancer were selected. Inclusion criteria consisted of CRF severity as an outcome and testing of exercise, psychological, exercise plus psychological, or pharmaceutical interventions.
  
  
  METHODS
  Studies were independently reviewed by 12 raters in 3 groups using a systematic and blinded process for reconciling disagreement. Effect sizes (Cohen d) were calculated and inversely weighted by SE.
  
  
  METHODS
  Severity of CRF was the primary outcome. Study quality was assessed using a modified 12-item version of the Physiotherapy Evidence-Based Database scale (range, 0-12, with 12 indicating best quality).
  
  
  RESULTS
  From 17 033 references, 113 unique studies articles (11 525 unique participants; 78% female; mean age, 54 [range, 35-72] years) published from January 1, 1999, through May 31, 2016, had sufficient data. Studies were of good quality (mean Physiotherapy Evidence-Based Database scale score, 8.2; range, 5-12) with no evidence of publication bias. Exercise (WES, 0.30; 95% CI, 0.25-0.36; P < .001), psychological (WES, 0.27; 95% CI, 0.21-0.33; P < .001), and exercise plus psychological interventions (WES, 0.26; 95% CI, 0.13-0.38; P < .001) improved CRF during and after primary treatment, whereas pharmaceutical interventions did not (WES, 0.09; 95% CI, 0.00-0.19; P = .05). Results also suggest that CRF treatment effectiveness was associated with cancer stage, baseline treatment status, experimental treatment format, experimental treatment delivery mode, psychological mode, type of control condition, use of intention-to-treat analysis, and fatigue measures (WES range, -0.91 to 0.99). Results suggest that the effectiveness of behavioral interventions, specifically exercise and psychological interventions, is not attributable to time, attention, and education, and specific intervention modes may be more effective for treating CRF at different points in the cancer treatment trajectory (WES range, 0.09-0.22).
  
  
  CONCLUSIONS
  Exercise and psychological interventions are effective for reducing CRF during and after cancer treatment, and they are significantly better than the available pharmaceutical options. Clinicians should prescribe exercise or psychological interventions as first-line treatments for CRF.
authors.affiliation: Department of Surgery, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Mustian
authors.affiliation: Behavioral Medicine Research Center, American Cancer Society, Washington, DC.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Alfano
authors.affiliation: Department of Surgery, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York.
authors.forename: Charles
authors.initials: C
authors.lastname: Heckler
authors.affiliation: Department of Surgery, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York.
authors.forename: Amber S
authors.initials: AS
authors.lastname: Kleckner
authors.affiliation: Department of Surgery, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Kleckner
authors.affiliation: Behavioral Medicine Research Center, American Cancer Society, Washington, DC.
authors.forename: Corinne R
authors.initials: CR
authors.lastname: Leach
authors.affiliation: Department of Preventive Medicine, Northwestern University, Rochester, New York.
authors.forename: David
authors.initials: D
authors.lastname: Mohr
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford Cancer Institute, Stanford University, Stanford, California.
authors.forename: Oxana G
authors.initials: OG
authors.lastname: Palesh
authors.affiliation: Department of Surgery, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York.
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Peppone
authors.affiliation: Department of Nursing, School of Health and Human Services, National University, San Diego, California.
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Piper
authors.affiliation: Department of Psychosocial and Biobehavioral Medicine, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: John
authors.initials: J
authors.lastname: Scarpato
authors.affiliation: Behavioral Medicine Research Center, American Cancer Society, Washington, DC.
authors.forename: Tenbroeck
authors.initials: T
authors.lastname: Smith
authors.affiliation: School of Health and Applied Human Sciences, University of North Carolina Wilmington.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Sprod
authors.affiliation: Department of Psychosocial and Biobehavioral Medicine, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Miller
mesh_terms: D001559:Benzhydryl Compounds / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy; D064699:Dexmethylphenidate Hydrochloride / Q000627:therapeutic use; D003913:Dextroamphetamine / Q000627:therapeutic use; D005081:Exercise Therapy; D005221:Fatigue / Q000209:etiology / Q000628:therapy*; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008774:Methylphenidate / Q000627:therapeutic use; D008775:Methylprednisolone / Q000627:therapeutic use; D000077408:Modafinil; D009369:Neoplasms / Q000150:complications*; D017374:Paroxetine / Q000627:therapeutic use; D011613:Psychotherapy; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D064690:Wakefulness-Promoting Agents / Q000627:therapeutic use*
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D064699:Dexmethylphenidate Hydrochloride; D003913:Dextroamphetamine; D005938:Glucocorticoids; D008774:Methylphenidate; D008775:Methylprednisolone; D000077408:Modafinil; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D064690:Wakefulness-Promoting Agents