Pilot study to determine the optimal dose of methylphenidate for an n-of-1 trial for fatigue in patients with cancer.
OBJECTIVE
In advanced cancer, the prevalence of fatigue is high and can be related to treatment or disease. Methylphenidate hydrochloride (MPH) is a central nervous system stimulant that has been used to palliate fatigue. There is no standard dose for MPH when used for this indication; recommended doses range from 5–20 + mg/d.


METHODS
To identify a dose to test formally in a subsequent n-of-1 trial of fatigue, we recruited patients with advanced cancer and a fatigue score of 4 or more on a 10-point scale. Following a 3-day baseline assessment, each patient titrated MPH at doses ranging from 5 mg/d to 15 mg twice daily at 3-day intervals. In a daily diary, patients recorded measures of fatigue, depression, toxicity, and symptom control.


RESULTS
Ten patients provided consent, 9 completed 8 days and 5 received maximum dose at day 15. Three patients were unwilling to increase the dose to maximum levels as they were satisfied with the response at a lower dose. Across all patients, there was a pattern of rapidly improving fatigue and depression scores to day 9 (5 mg twice daily), with minimal improvement thereafter.


CONCLUSIONS
The results indicate a dose of 5 mg twice daily for the definitive study. There was little correlation between performance status and maximum tolerated dose. No patient withdrew because of toxicity.
Hardy
Janet Rea
JR
Department of Palliative Care, Mater Health Services, Mater Adult Hospital, Brisbane, Queensland, Australia.
Carmont
Sue-Ann S
SA
O'Shea
Angela
A
Vora
Rohan
R
Schluter
Philip
P
Nikles
Catherine Jane
CJ
Mitchell
Geoffrey Keith
GK
D000368:Aged; D000369:Aged, 80 and over; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D010865:Pilot Projects; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D008774:Methylphenidate