Naproxen reduces chemotherapy and pegfilgrastim-induced sleep disturbance possibly mediated through reduced bone pain

Abstract

Cancer treatment-related pain can cause sleep disturbance (SD). Recently, we reported that co-administration of the NSAID, naproxen, reduces pegfilgrastim-induced bone pain. The purpose of this secondary analysis was to determine if naproxen decreased SD and if this effect was mediated through changes in pain. The University of Rochester Cancer Center Community Clinical Oncology Program Research Base randomized 510 patients to receive naproxen or placebo simultaneously with pegfilgrastim administration. Patients recorded pain severity (0-10 VAS) for the subsequent 5 days. The area under the curve was calculated as the primary pain outcome. Both prior to and 5 days post PEG treatment, patients rated their SD (0-10 VAS). The mean post-treatment SD score was 3.74 [95% CI: 3.33, 4.15] in the placebo group and 2.92 [2.51, 3.32] in the naproxen group, representing a 22% decrease in the naproxen group. There was no difference in SD prior to treatment. NSAIDs have proven analgesic efficacy but no efficacy in SD prevention outside of painful contexts. Structural equation modeling was performed to assess the mediation effect of pain changes on naproxen-induced changes in SD. In this model, naproxen intervention was significantly predictive of decreased pain (path coefficient (PC) = −0.143 [−0.240, −0.045]), and changes in pain significantly predicted changes in SD (PC = 0.180 [0.123, 0.236]). The mediation effect of pain on SD was significant (indirect effect -0.026 [-0.048, −0.009]) while the direct effect of naproxen on sleep was not (PC = −.067 [−0.125, 0.008]). However, results were similar when SD was modeled as a mediator of pain; therefore, no definitive cause and effect relationship can be established statistically. These data suggest that co-administration of naproxen with pegfilgrastim can simultaneously reduce bone pain and SD. This treatment combination has the potential to minimize the damaging effects of pegfilgrastim on QOL and promote chemotherapy adherence.