Escalante, C.P., Meyers, C., Reuben, J.M., Wang, X., Qiao, W., Manzullo, E., . . . Cleeland, C. (2014). A randomized, double-blind, 2-period, placebo-controlled crossover trial of a sustained-release methylphenidate in the treatment of fatigue in cancer patients. Cancer Journal, 20(1), 8–14.

To assess effectiveness of methylphenidate versus placebo to reduce cancer-related fatigue and to analyze cytokine levels and symptoms of cognitive function

Patients were randomized to receive either methylphenidate 18 mg per day for two weeks followed by placebo for two weeks, or to receive placebo for the first two weeks followed by methylphenidate for three weeks. All completed a battery of tests at baseline and were asked to record fatigue level and interference with activities in a daily diary. Additional fatigue measurement occurred at week 1 and week 3. Bloodwork for cytokine levels was obtained at baseline, crossover, and the end of the study.

• N = 33
• MEAN AGE = 57 years (range 32–79 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer; 74% had metastatic disease; 84% were currently on chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: 74% were white; 68% had more than high school education; 52% were working full-time or part-time.

• SITE: Single site
• SETTING TYPE: Outpatient    
• LOCATION: MD Anderson Cancer Center, Texas

PHASE OF CARE: Multiple phases of care

Double-blind, placebo-controlled crossover RCT

• Wechsler Adult Intelligence Scale (WAIS)
• Digit Span and Digit Symbol Tests
• Hopkins Verbal Learning Test
• Controlled Oral Word Association
• Trial Making Test Parts A and B
• Grooved Pegboard Test
• Brief Fatigue Inventory (BFI)
• Beck Depression Inventory II
• Brief Sleep Disturbance Scale
• Profile of Mood States (POMS)
• MD Anderson Symptom Inventory
• Work Productivity and Impairment Questionnaire (WPAI)
• Multiple inflammatory cytokine levels

There were no significant differences between treatment arms for fatigue by BFI scores or diaries. There was no carryover effect of methylphenidate, so data were pooled for analysis. There were no differences in symptom inventory results. The WAIS-III digit span test demonstrated improved cognitive processing speed in the treatment versus placebo condition (p = .01), and the subscale of confusion on POMS was lower with methylphenidate (p = .05). There was a significant correlation between BFI interference and activity level and the Hopkins Verbal Learning Test showing declining memory with higher levels of fatigue (p < .05).  Patients receiving methylphenidate missed fewer hours of work due to health (p = .03). There were no significant differences in or correlations with cytokine levels. There were no serious adverse events with methylphenidate.

This study did not show improvement in fatigue with methylphenidate. Findings suggest that some aspects of cognitive function are related to fatigue level.

• Small sample (< 100)
• Other limitations/explanation: The study was underpowered.

Findings do not show that methylphenidate improved fatigue symptoms, but it may have had some effect on missing work and some aspects of cognitive function. Further exploration of associations between fatigue and cognitive impairment associated with chemotherapy is warranted.