Managing fatigue with methylphenidate and physical activity during cancer immunotherapy treatment

Despite the high frequency and severity of fatigue among patients with advanced cancer receiving immunotherapy, there are limited treatment options available. The aim of the study was to explore the effects of the methylphenidate (MP) with standardized physical activity (PA) on cancer related fatigue (CRF).

In this pilot study, patients with advanced cancer with clinically significant CRF (<34 on Functional Assessment of Cancer Illness Therapy - fatigue scale, FACIT-F), on anti-PD1 immunotherapy were eligible. Patients were randomized to standardized PA with either patient-controlled MP 5 mg (MP + PA arm) or matching Placebo (Pl + PA arm) twice daily for 14 days. The primary outcome was the change in the FACIT-F score. Secondary outcomes included changes in fatigue dimensions (Multidimensional Fatigue Symptom Inventory-Short Form (MSFI-SF), Functional Assessment of Cancer Therapy - General (FACT-G), Patient-Reported Outcome Measurement Information System-Fatigue (PROMIS-F), and hospital anxiety and Depression Scale (HADS).

Of the 40 randomized patients, 34 were evaluable. The FACIT-F scores significantly improved in both the arms with mean (SD) change, effect size (ES) of 11(14), 0.87(P < .001); and 9(12), 0.74(P = .04) in MP + PA, and Pl + PA arms respectively. We also found significant improvements in PROMIS-F, ES - 1.05(P = .003), MFSI-SF(global), ES - 1.32(P < .001), and HADS-depression, ES - 0.92(P = .004) in the MP + PA arm; There were no significant differences in adverse events between groups.

Our preliminary study found MP + PA was associated with significant improvement in CRF scores. The fatigue dimensions and depression scores significantly improved in the MP + PA arm. Further comparative studies using MP + PA for CRF are justified.