Butler, J.M., Jr., Case, L.D., Atkins, J., Frizzell, B., Sanders, G., Griffin, P., … Shaw, E.G. (2007). A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy. International Journal of Radiation Oncology, Biology, Physics, 69(5), 1496–1501.

This study was conducted to assess the effect of prophylactic d-methylphenidate HCl (d-MPH), a central nervous system stimulant, on quality of life and cognitive function in patients with brain tumors undergoing radiation therapy.

The treatment group received a starting dose of 5 mg twice daily of d-MPH; this was escalated to a maximum of 15 mg twice daily. Patients were stratified by tumor type (primary versus metastatic), treatment (radiation therapy alone versus radiation therapy plus chemotherapy), and Karnofsky Performance Status (< 90 versus 90), and were randomized within strata to one of the two treatment arms.

• The total number of participants was 68. 
• There were 34 participants in the treatment group and 34 in the placebo group.  
• The median age of the treatment group was 52, with a range of 31–79.
• The median age of the placebo group was 60, with a range of 28–83. 
• 54.4% of participants were male and 45.6% were female, distributed across each group.
• 48.5% of participants had primary brain cancer and 51.5% had metastatic brain cancer.

This was a randomized, double-blind, placebo-controlled study.

• Mini-Mental State Examination (MMSE) for global cognitive functioning
• Functional Assessment of Cancer Therapy (FACT)-Brain for cancer-related quality of life specific to patients with brain tumors
• Functional Assessment of Cancer Therapy-F for cancer-related quality of life pertaining to symptom of fatigue
• Center for Epidemiologic Studies-Depression Scale (CES-D) for depressive symptoms

There was no difference in cognitive functioning at baseline, end of radiation therapy, or at 4, 8, and 12 weeks after brain radiation therapy. No difference in fatigue or quality of life was observed. 

Prophylactic use of d-MPH in patients with brain tumors undergoing radiation therapy did not result in an improvement in cognitive functioning, quality of life, or fatigue.

• The study's primary outcome was fatigue.
• The study had limited measurement of cognitive function; the MMSE is a global indicator.
• There was a small sample size and a high dropout rate. Only 47% of participants completed the eight-week assessment.
• The study was stopped prematurely because of slow accrual and stoppage of funding by the sponsoring drug company.
• Four patients (6%) experienced side effects; two experienced nausea and vomiting, one experienced tachycardia on the placebo arm, and one went off the study due to an increase in liver enzymes.