A randomized, double-blind, 2-period, placebo-controlled crossover trial of a sustained-release methylphenidate in the treatment of fatigue in cancer patients.
OBJECTIVE
This study assessed the efficacy of methylphenidate versus placebo for cancer-related fatigue reduction. Other objectives were to analyze cytokine levels and to determine the effects of methylphenidate on other symptoms, cognitive function, work yield, and patients' perceptions and preferences.


METHODS
Patients were randomly assigned (1:1) to receive methylphenidate-placebo or placebo-methylphenidate for 4 weeks. Patients crossed over after 2 weeks. Wilcoxon signed rank tests and McNemar tests were used to assess continuous and categorical variables. The primary efficacy endpoint was change in the level of worst fatigue on the Brief Fatigue Inventory (BFI) at the end of each 2-week period.


RESULTS
The mean baseline BFI score was moderate (5.7). Methylphenidate treatment did not affect patients' worst level of fatigue or other symptoms. Results from the Wechsler Adult Intelligence Scale Digit Symbol Test and the Hopkins Verbal Learning Test with BFI interference questions and BFI activity questions showed significant improvement in the methylphenidate-treated patients' verbal learning, memory, visual perception, analysis, and scanning speed. Patients treated with methylphenidate missed significantly fewer work hours owing to health reasons and worked significantly more hours. After 4 weeks, 64% of patients reported that methylphenidate improved their cancer-related fatigue, and 58% wanted to continue treatment. Significant difference in interleukin 6R (positive), interleukin 10 (negative), and tumor necrosis factor α (positive) was noted between the methylphenidate and the placebo group.


CONCLUSIONS
Low-dose methylphenidate did not improve cancer-related fatigue. Patients taking methylphenidate had better cognition and were able to work more hours. Patients tolerated methylphenidate well, and the majority felt better and wanted to continue treatment.
From the *The University of Texas MD Anderson Cancer Center, Houston, TX; and †Hematology/Oncology Therapeutic Area, Amgen, Thousand Oaks, CA.
Carmen P
CP
Escalante
Christina
C
Meyers
James M
JM
Reuben
Xuemei
X
Wang
Wei
W
Qiao
Ellen
E
Manzullo
Ricardo H
RH
Alvarez
Phuong Khanh
PK
Morrow
Ana M
AM
Gonzalez-Angulo
Xin Shelley
XS
Wang
Tito
T
Mendoza
Wenli
W
Liu
Holly
H
Holmes
Jessica
J
Hwang
Katherine
K
Pisters
Michael
M
Overman
Charles
C
Cleeland
D000328:Adult; D000368:Aged; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; 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* / Q000188:drug therapy; D010919:Placebos
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D010919:Placebos; D008774:Methylphenidate