Dexamethasone Plus Physical Activity May Reduce Cancer-Related Fatigue

Combining physical activity with dexamethasone has led to clinically significant improvements in fatigue and quality of life.

A combination of physical activity and dexamethasone showed clinically significant improvements in cancer-related fatigue and quality of life for patients with advanced cancer, as demonstrated by a recent study.

“We observed a sustained improvement in [cancer-related fatigue] and fatigue-related outcomes for up to 3 weeks compared with baseline after discontinuation of [dexamethasone], suggesting that possible priming effects of [dexamethasone] helped sustain [physical activity],” reported researchers at The University of Texas MD Anderson Cancer Center in Houston, which was responsible for the study (NCT03583255).¹ Of note, the study was published in the Journal of the National Comprehensive Cancer Network.

Patients in the study had advanced cancer and a cancer-related fatigue score of 4 or higher according to the Edmonton Symptom Assessment Scale (ESAS) for fatigue, which grades on a scale from 0 to 10. Patients were given a standardized regimen of aerobic and resistance-based physical activity to follow for 28 days. In addition, patients were randomized to 4 mg of dexamethasone or placebo for the first 7 days of the physical activity schedule. Participants were evaluated for indicators of cancer-related fatigue from baseline to on days 8 and 29, one day after ending medication and physical activity programs, respectively. Fatigue scores significantly improved in the dexamethasone group. Patients saw a median improvement in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores of 9 (range, 2-16; P < .001) on day 8 and 5.75 (range, 0-12.5; P = .015) on day 29, with effect sizes of -3.49 and -2.43, respectively. Patients assigned placebo experienced median changes in these scores of 3.5 (range, -2.1 to 10; P = .054) at day 8 and 6.5 (range, 2.5-15.5; P = .006) by day 29.

In all other metrics for cancer-related fatigue, only the patients who received dexamethasone experienced significant results and did so on days 8 and 29.

From baseline to day 8, patients assigned physical activity and dexamethasone had the following median changes in scores: -2 (IQR, -3 to 0; P = .001) for the Edmonton Symptom Assessment Scale (ESAS Fatigue); -7.9 (IQR, -12 to 0; P = .003) for the Patient Reported Outcomes Measurement Information System-Fatigue Short Form 7a (PROMIS-Fatigue SF-7a), and -8 (IQR, -16 to 1; P = .023) for Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) scores. In comparison, the median change scores from baseline to day 8 in the placebo group were 0 (IQR, -2 to 1; P = .23) for ESAS Fatigue, -1.4 (IQR, -8.3 to 4.2; P = .09) for PROMIS-Fatigue SF-7a, and -3.5 (IQR, -9 to 3; P = .26) for MFSI-SF total.

From baseline to day 29, the median change score for patients assigned dexamethasone was -1 (IQR, -2 to 0; P = .015) for ESAS Fatigue, -5.45 (IQR, -8.8 to 0; P = .005) for PROMIS-Fatigue SF-7a, and -11 (IQR, -21 to 4; P = .007) for MFSI-SF total. For the placebo arm, the median change scores were 0 (IQR, -4 to 1; P = .07) for ESAS Fatigue, -4.25 (IQR, -9.8 to 1.7; P = .14) for PROMIS-Fatigue SF-7a, and -7.5 (IQR, -16 to 3; P = .094) for MFSI-SF total.

Quality of life, as measured by FACT-G, increased in both groups, but improvements were statistically significant for those whose physical activity were paired with dexamethasone.

Those whose took dexamethasone experienced a median improvement in FACT-G scores from intake of 5.5 (IQR, -0.8 to 12; P = .017) on day 8 and a median improvement of 6.97 (IQR, 3-10.5; P = .001) on day 29, compared with the placebo group’s median improvement of 2.17 (IQR, -3.83 to 10; P = .14) on day 8 and 3.09 (IQR, -3.75 to 10; P = .094) on day 29.

FACT-G physical wellbeing (PWB) scores improved significantly for patients in the dexamethasone group on both days 8 and 29, with median improvements of 3 (IQR, 0-5; P = .001) and 2 (IQR, 1-4; P = .002), respectively. Scores for those in the placebo group also significantly improved on day 8, with a median improvement of 2 (IQR, -1 to 3; P = .049), although there was no change at day 29 (IQR, -1 to 3; P = .15).

“These results may suggest a possible impact of combination [physical activity and dexamethasone] more on the peripheral rather than the central causes, such as reduction of inflammatory components of [cancer-related fatigue],” the study authors wrote. “However, more research is necessary.”

A total of 13 serious adverse events (AEs) occurred during the study, with 6 occurring in the dexamethasone group and 7 in the placebo group. No significant difference in rates of serious AEs was observed between the two patient groups (P = .36). One AE—a case of grade 3 insomnia—was possibly related to physical activity plus dexamethasone.

Researchers analyzed the effects of this regimen in 64 patients. The adherence rates for the dexamethasone and placebo groups were 91% and 92%, respectively for study medication (P = .15), 83% and 70.6% for resistance exercise (P = .35), and 82.9% and 78.3% for aerobic exercise (P = .73).

High rates of satisfaction, as assessed by a 5-point scale, were associated with both groups. The dexamethasone arm reported a 98% satisfaction rate, and the placebo arm reported a 79% satisfaction rate.

Reference

Yennurajalingam S, Valero V, Smalgo BG, et al. Physical Activity and Dexamethasone for Cancer-Related Fatigue: A Preliminary Placebo-Controlled, Randomized, Double-Blind Trial. J Natl Compr Canc Netw. Published online January 7, 2025. doi:10.6004/jnccn.2024.7071