Methylphenidate to Improve Quality of Life in Patients Undergoing Radiation Therapy for Brain Tumors

OBJECTIVES:

- Determine the effect of d-methylphenidate on fatigue in patients receiving radiotherapy
for primary or metastatic brain tumors.

- Determine the effect of this drug on the quality of life of these patients.

- Determine the effect of this drug on depression in these patients.

- Determine the effect of this drug on global neurocognitive function, including attention
and concentration, memory, language, visuospatial skills, and executive function, in
these patients.

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients
are stratified by tumor type (primary vs metastatic), treatment (radiotherapy vs radiotherapy
and chemotherapy), and Karnofsky performance status (70% or 80% vs 90% or 100%). Patients are
randomized to one of two treatment arms.

All patients undergo radiotherapy over weeks 1-4.

- Arm I: Patients receive oral d-methylphenidate twice daily on weeks 1-12.

- Arm II: Patients receive oral placebo twice daily on weeks 1-12. In both arms, quality
of life is assessed at baseline, at the end of radiotherapy, and at 4, 8, and 12 weeks
after radiotherapy.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 200 patients (100 per treatment arm) will be accrued for this
study within 18 months.

DISEASE CHARACTERISTICS:

- Histologically confirmed metastatic brain tumor OR

- Histologically confirmed primary brain tumor

- Glioblastoma multiforme

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- Anaplastic mixed oligoastrocytoma

- Low-grade glioma

- Meningioma

- Ependymoma

- Planned external beam cranial radiotherapy (partial or whole brain) with a total dose
of at least 25 Gy in at least 10 fractions of 180-300 cGy each

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Karnofsky 70-100%

Life expectancy:

- At least 3 months

Hematopoietic:

- WBC ≥ 1,500/mm^3

- Hemoglobin ≥ 10.0 g/dL

- Platelet count ≥ 75,000/mm^3

Hepatic:

- Not specified

Renal:

- Not specified

Cardiovascular:

- No hypertension or other cardiovascular disease requiring antihypertensives and/or
other cardiovascular medications

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other serious medical or psychiatric illness that would preclude study
participation

- No hypersensitivity to study drug

- No history of steroid psychosis

- No family history of or active Tourette's Syndrome

- No prior or active glaucoma

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- Prior or concurrent chemotherapy allowed

Endocrine therapy:

- Concurrent steroids allowed

Radiotherapy:

- See Disease Characteristics

- Prior radiotherapy allowed except to brain (including stereotactic radiosurgery)

- No concurrent craniospinal axis radiotherapy

Surgery:

- Not specified

Other:

- No prior or concurrent medications for attention deficit disorder, anxiety disorder,
schizophrenia, or substance abuse

- No concurrent anti-depressants