Multimodal therapy for cancer related fatigue in patients with prostate cancer receiving radiotherapy and androgen deprivation therapy

Background: There are limited studies to evaluate treatments that target causative mechanisms of Cancer-related-fatigue (CRF) using validated tools in a defined population. The objective is to determine the feasibility, and the preliminary estimates of the effects of various combinations of standardized exercise, cognitive behavioral therapy (CBT), and methylphenidate (multimodal therapy, or MMT) on CRF as measured by AUC of Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) subscale scores in Pts with prostate cancer receiving radiotherapy with androgen deprivation therapy. Methods: Prostate cancer Pts with CRF scheduled to receive radiotherapy with androgen deprivation therapy were eligible. Using a double blind (patient, investigators) randomized factorial study design, eligible Pts were randomized into 1 of the 8 arms, which included all possible combinations of the interventions (exercise, CBT, and methylphenidate) and/or their corresponding placebo treatments for a duration of 8 weeks. Results: 62/69 (89%) randomized Pts were evaluable. There were no differences in the demographics and baseline fatigue between groups. The adherence rates for pills, exercise and CBT were 96.5%, 67%, and 90% respectively. The study was feasible and there was no significant difference in adverse events by groups. Table 1 shows the comparison of AUC by treatment. For Pts receiving drug compared to placebo, the median FACIT-F AUC was 2328 vs 2095. The drug effect (estimate, 95% CI) in Pts who received Exercise was 596 (68.3, 1125); CBT was 354 (-121, 830); combined Exercise and CBT was -187 (-802,427); and control Exercise, control CBT was 294 (-192,781). Conclusions: Methylphenidate containing combinations were superior to no drug combinations. Methylphenidate + Exercise provided the best signal and should proceed to large randomized control trials. (Table Presented).