Nationwide randomized, phase III, placebo-controlled trial of bupropion for cancer-related fatigue: Primary outcome results.

LBA12003 Background: Fatigue is common and debilitating among people with cancer. Treatment options for cancer-related fatigue are limited. Methylphenidate demonstrates limited efficacy and low tolerability. Behavioral interventions include exercise and cognitive-behavioral therapy, which many individuals may be unwilling or unable to adopt. Additional therapies are needed. Bupropion has been shown to reduce two hypothesized mechanisms of cancer-related fatigue (CRF), systemic inflammation and hypothalamic pituitary adrenal (HPA) axis functioning. A large-scale, placebo-controlled evaluation of bupropion is needed to offer a potential new therapeutic option for CRF. Methods: The trial was conducted through the University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program (URCC NCORP) Research Base and member sites across the U.S. Eligible patients were adults with any stage or site of disease who reported moderate to severe worst fatigue (i.e., score of 4 or above on 0-10 scale) in past week and had no reported or documented contraindication to bupropion. They completed surgery, radiation, and/or intravenous (IV) anticancer therapy at least two months prior to enrollment. Individuals receiving oral therapies or IV supportive therapy were eligible. Participants were randomized 1:1 to receive over-encapsulated 150 mg bupropion or a placebo. They were instructed to take one capsule in week 1, two capsules in weeks 2-12, and one capsule in week 13. The primary outcome was group differences in the FACIT-F fatigue subscale score at week 12. ANCOVA was conducted with group as the main factor and baseline FACIT-F score as a covariate. Study site was included as a random effect independent of residual error. The study was designed with a statistical power of 90% to identify a difference of 0.30 SD in the FACIT-F score, which corresponds to a clinically meaningful change. Results: Participants (N = 428) had a mean age of 61 years (SD = 12). Most were female (83%), white (86%), non-Hispanic (93%), and/or diagnosed with breast cancer (73%). There were no baseline group differences in demographic, clinical, or fatigue variables ( p values>0.13), except the bupropion group was less likely to have received radiation (65% vs. 74%, p = 0.05). Intent-to-treat analyses indicated that bupropion significantly reduced fatigue (Cohen’s d = 0.23, p = 0.03) relative to placebo. Prespecified moderator analyses indicated that bupropion was associated with significant improvements in fatigue in women (Cohen’s d = 0.33, p = 0.006) but not men ( p = 0.24). Conclusions: In this large, phase III, community-based trial, bupropion resulted in modest reductions in fatigue relative to placebo, particularly among women. Bupropion should be considered in the pharmacologic management of CRF. Clinical trial information: NCT03996265 .