Patient Controlled Administration of Methylphenidate for Cancer Related Fatigue - PRN Methylphenidate

Fatigue is a major problem in cancer patients. Methylphenidate is a drug currently FDA
approved for the treatment of attention deficit disorder and narcolepsy (sleep disorder).
Methylphenidate has shown a benefit in improving thinking and decreasing drowsiness and pain
in cancer patients taking opioids (pain killers). Methylphenidate has also shown a rapid
response in treating depression.

Participants in this study will at first have an evaluation of their fatigue, ability to
sleep, and they will answer a set of general symptom questions. It will take about 20 minutes
to complete the evaluation. Participants will have a blood test called TSH
(thyroid-stimulating hormone) performed to rule out the possibility of thyroid dysfunction as
cause of fatigue.

The study will last for 7 days. Participants will be able to take up to four methylphenidate
tablets a day on an as needed basis for fatigue. Participants will keep a daily diary where
they will record their fatigue rating (0-10) before and 2 hours after taking methylphenidate.
The research nurse will contact participants daily by phone (in person for in-patients) to
make sure the daily diary is being filled out, to ask about side effects of treatment, and to
ask participants to rate their fatigue at four times during the past day and about any
possible causes of fatigue.

On the 7th day of treatment, participants will be evaluated in the palliative care clinic or
by telephone. Evaluation of fatigue, ability to sleep, and general symptoms along with an
evaluation of side effects and effectiveness of methylphenidate will be performed. The
evaluation will take about 15 minutes to complete. If participants develop intolerable side
effects while on study, the medication will be stopped and they will be removed from the
study.

If participants find the drug beneficial and wish to continue taking it, they will be given a
prescription for methylphenidate and can be followed as an outpatient in the palliative care
clinic. Participants who choose to continue the medication will be evaluated at the end of 4
weeks for fatigue, ability to sleep, and general symptoms along with an evaluation of side
effects and effectiveness by phone or in the clinic. The evaluation will take about 15
minutes to complete.

This is an investigational study. The use methylphenidate is investigational. A total of 36
patients will take part in this study. All will be enrolled at UTMDACC.

Inclusion Criteria:

1. Patients seen in the outpatient palliative care clinic or inpatients seen by the
palliative care consult team or the fatigue clinic.

2. Presence of fatigue on a numerical scale during the last 24 hours of more or equal to
4 on a 0 to 10 scale on which 0 equals no fatigue and 10 worst possible fatigue.

3. Patient should describe fatigue as being present for a minimum of four days.

4. If patients are on opioids for the treatment of cancer pain, they must have had no
dose changes (>25%) for at least 48 hours prior to study entry. Change in opioid dose
after study entry is allowed.

5. Presence of relatively intact cognition defined by normal Mini Mental State
Questionnaire according to age and education level. A score of 24 or above is usually
considered normal.

6. Signed written informed consent.

7. Patient must be 18 years or older.The questionnaires used in this study have been
validated only in the adult population.

8. Patient willing to keep a daily fatigue diary, engage in daily telephone follow up
with a nurse and after 7 days of treatment either return for a follow up visit or this
can be done over the telephone.

9. Hemoglobin of >/=10 g/dl within 2 weeks of enrollment. If the patient has not had
blood drawn for a hemoglobin level in the past two weeks, one will be done to
determine the eligibility.

Exclusion Criteria:

1. Major contraindication to methylphenidate i.e. hypersensitivity

2. Currently on methylphenidate or has been on methylphenidate within the last 10 days.

3. Inability to complete the baseline assessment forms or to understand the
recommendations for participation in the study.

4. Pregnant or lactating women. Childbearing age women are not on birth control.

5. Patients taking MAO inhibitors, tricyclic antidepressants, clonidine,
psychostimulants, concurrent steroids or other medications specifically for fatigue

6. Patients with glaucoma, history of marked anxiety disorder, or history of substance
abuse.

7. CAGE questionnaire score is 2 or above on a 0 to 4 scale.

8. Patients with history of seizures or uncontrolled CNS disease, significant hepatic or
renal dysfunction.