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.