title: Fatigue in patients with advanced renal cell carcinoma receiving sunitinib on an intermittent versus continuous dosing schedule in a randomized phase II trial.
abstract: A phase II trial in advanced renal cell carcinoma (RCC) found no benefit in efficacy or safety between patients receiving oral sunitinib 50 mg/day for 4 weeks followed by 2-week off-treatment (Schedule 4/2) and those receiving 37.5 mg continuous daily sunitinib. We hypothesized that fatigue would have a more variable "on-off" effect with the 4/2 schedule. A total of 292 patients completed two fatigue-related items on Days 1 and 29 of each treatment cycle. Mean absolute slopes were compared across treatments. A planned analysis of item "I feel fatigued" demonstrated that the mean absolute slope was greater in Schedule 4/2 compared to continuous dosing (0.042 vs. 0.032, P = 0.003), and analysis based on the change from Day 1 to Day 29 (0.52 vs. 0.21, P = 0.002) and, separately, Day 29 to the next Day 1 (-0.38 vs. -0.05, P < 0.001) showed the changes to be significantly larger in Schedule 4/2 than continuous dosing. "I have a lack of energy" showed a similar pattern graphically, however, the planned analysis was not statistically significant based on the absolute slopes but was when Day 1 to Day 29 and Day 29 to Day 1 changes were analyzed separately. The 4/2 arm was associated with a greater degree of variability in fatigue reflecting a possible "on-off" effect whereby patients receiving the 4/2 schedule reported less fatigue at the beginning of each cycle compared to Day 29. The findings can inform care for individuals with advanced RCC receiving intermittent dosing of sunitinib.
authors.affiliation: Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.
authors.forename: David
authors.initials: D
authors.lastname: Cella
authors.forename: Sally E
authors.initials: SE
authors.lastname: Jensen
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hahn
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Beaumont
authors.forename: Beata
authors.initials: B
authors.lastname: Korytowsky
authors.forename: Helen
authors.initials: H
authors.lastname: Bhattacharyya
authors.forename: Robert
authors.initials: R
authors.lastname: Motzer
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D017322:Clinical Trials, Phase II as Topic; D004334:Drug Administration Schedule; D005221:Fatigue / Q000175:diagnosis* / Q000209:etiology*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D009367:Neoplasm Staging; D011758:Pyrroles / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D057566:Self Report; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Fatigue; quality of life; renal cell carcinoma; sunitinib