Modafinil for the treatment of fatigue in lung cancer: results of a placebo-controlled, double-blind, randomized trial.
OBJECTIVE
Fatigue is a distressing symptom occurring in more than 60% of patients with cancer. The CNS stimulants modafinil and methylphenidate are recommended for the treatment of cancer-related fatigue, despite a limited evidence base. We aimed to evaluate the efficacy and tolerability of modafinil in the management of fatigue in patients with non-small-cell lung cancer (NSCLC).


METHODS
Adults with advanced NSCLC and performance status of 0 to 2, who were not treated with chemotherapy or radiotherapy within the last 4 weeks, were randomly assigned to daily modafinil (100 mg on days 1 to 14; 200 mg on days 15 to 28) or matched placebo. The primary outcome was change in Functional Assessment of Chronic Illness Therapy (FACIT) -Fatigue score from baseline to 28 days, adjusted for baseline fatigue and performance status. Secondary outcomes included safety and patient-reported measures of depression, daytime sleepiness, and quality of life.


RESULTS
A total of 208 patients were randomly assigned, and 160 patients (modafinil, n = 75; placebo, n = 85) completed questionnaires at both baseline and day 28 and were included in the modified intention-to-treat analysis. FACIT-Fatigue scores improved from baseline to day 28 (mean score change: modafinil, 5.29; 95% CI, 2.57 to 8.02; placebo, 5.09; 95% CI, 2.54 to 7.65), but there was no difference between treatments (0.20; 95% CI, -3.56 to 3.97). There was also no difference between treatments for the secondary outcomes; 47% of the modafinil group and 23% of the placebo group stated that the intervention was not helpful.


CONCLUSIONS
Modafinil had no effect on cancer-related fatigue and should not be prescribed outside a clinical trial setting. Its use was associated with a clinically significant placebo effect.
Anna Spathis and Kate Fife, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Fiona Blackhall, The Christie NHS Foundation Trust and University of Manchester, Manchester; Susan Dutton, Ronja Bahadori, Rose Wharton, and Bee Wee, University of Oxford; Bee Wee, Sir Michael Sobell House, Oxford; Mary O'Brien, Royal Marsden Hospital; Patrick Stone, St George's University of London; Tim Benepal, St George's Hospital NHS Trust, London; and Nick Bates, Buckinghamshire Healthcare NHS Trust, Aylesbury, United Kingdom. aspathis@doctors.org.uk.
Anna
A
Spathis
Anna Spathis and Kate Fife, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Fiona Blackhall, The Christie NHS Foundation Trust and University of Manchester, Manchester; Susan Dutton, Ronja Bahadori, Rose Wharton, and Bee Wee, University of Oxford; Bee Wee, Sir Michael Sobell House, Oxford; Mary O'Brien, Royal Marsden Hospital; Patrick Stone, St George's University of London; Tim Benepal, St George's Hospital NHS Trust, London; and Nick Bates, Buckinghamshire Healthcare NHS Trust, Aylesbury, United Kingdom.
Kate
K
Fife
Anna Spathis and Kate Fife, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Fiona Blackhall, The Christie NHS Foundation Trust and University of Manchester, Manchester; Susan Dutton, Ronja Bahadori, Rose Wharton, and Bee Wee, University of Oxford; Bee Wee, Sir Michael Sobell House, Oxford; Mary O'Brien, Royal Marsden Hospital; Patrick Stone, St George's University of London; Tim Benepal, St George's Hospital NHS Trust, London; and Nick Bates, Buckinghamshire Healthcare NHS Trust, Aylesbury, United Kingdom.
Fiona
F
Blackhall
Anna Spathis and Kate Fife, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Fiona Blackhall, The Christie NHS Foundation Trust and University of Manchester, Manchester; Susan Dutton, Ronja Bahadori, Rose Wharton, and Bee Wee, University of Oxford; Bee Wee, Sir Michael Sobell House, Oxford; Mary O'Brien, Royal Marsden Hospital; Patrick Stone, St George's University of London; Tim Benepal, St George's Hospital NHS Trust, London; and Nick Bates, Buckinghamshire Healthcare NHS Trust, Aylesbury, United Kingdom.
Susan
S
Dutton
Anna Spathis and Kate Fife, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Fiona Blackhall, The Christie NHS Foundation Trust and University of Manchester, Manchester; Susan Dutton, Ronja Bahadori, Rose Wharton, and Bee Wee, University of Oxford; Bee Wee, Sir Michael Sobell House, Oxford; Mary O'Brien, Royal Marsden Hospital; Patrick Stone, St George's University of London; Tim Benepal, St George's Hospital NHS Trust, London; and Nick Bates, Buckinghamshire Healthcare NHS Trust, Aylesbury, United Kingdom.
Ronja
R
Bahadori
Anna Spathis and Kate Fife, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Fiona Blackhall, The Christie NHS Foundation Trust and University of Manchester, Manchester; Susan Dutton, Ronja Bahadori, Rose Wharton, and Bee Wee, University of Oxford; Bee Wee, Sir Michael Sobell House, Oxford; Mary O'Brien, Royal Marsden Hospital; Patrick Stone, St George's University of London; Tim Benepal, St George's Hospital NHS Trust, London; and Nick Bates, Buckinghamshire Healthcare NHS Trust, Aylesbury, United Kingdom.
Rose
R
Wharton
Anna Spathis and Kate Fife, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Fiona Blackhall, The Christie NHS Foundation Trust and University of Manchester, Manchester; Susan Dutton, Ronja Bahadori, Rose Wharton, and Bee Wee, University of Oxford; Bee Wee, Sir Michael Sobell House, Oxford; Mary O'Brien, Royal Marsden Hospital; Patrick Stone, St George's University of London; Tim Benepal, St George's Hospital NHS Trust, London; and Nick Bates, Buckinghamshire Healthcare NHS Trust, Aylesbury, United Kingdom.
Mary
M
O'Brien
Anna Spathis and Kate Fife, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Fiona Blackhall, The Christie NHS Foundation Trust and University of Manchester, Manchester; Susan Dutton, Ronja Bahadori, Rose Wharton, and Bee Wee, University of Oxford; Bee Wee, Sir Michael Sobell House, Oxford; Mary O'Brien, Royal Marsden Hospital; Patrick Stone, St George's University of London; Tim Benepal, St George's Hospital NHS Trust, London; and Nick Bates, Buckinghamshire Healthcare NHS Trust, Aylesbury, United Kingdom.
Patrick
P
Stone
Anna Spathis and Kate Fife, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Fiona Blackhall, The Christie NHS Foundation Trust and University of Manchester, Manchester; Susan Dutton, Ronja Bahadori, Rose Wharton, and Bee Wee, University of Oxford; Bee Wee, Sir Michael Sobell House, Oxford; Mary O'Brien, Royal Marsden Hospital; Patrick Stone, St George's University of London; Tim Benepal, St George's Hospital NHS Trust, London; and Nick Bates, Buckinghamshire Healthcare NHS Trust, Aylesbury, United Kingdom.
Tim
T
Benepal
Anna Spathis and Kate Fife, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Fiona Blackhall, The Christie NHS Foundation Trust and University of Manchester, Manchester; Susan Dutton, Ronja Bahadori, Rose Wharton, and Bee Wee, University of Oxford; Bee Wee, Sir Michael Sobell House, Oxford; Mary O'Brien, Royal Marsden Hospital; Patrick Stone, St George's University of London; Tim Benepal, St George's Hospital NHS Trust, London; and Nick Bates, Buckinghamshire Healthcare NHS Trust, Aylesbury, United Kingdom.
Nick
N
Bates
Anna Spathis and Kate Fife, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge; Fiona Blackhall, The Christie NHS Foundation Trust and University of Manchester, Manchester; Susan Dutton, Ronja Bahadori, Rose Wharton, and Bee Wee, University of Oxford; Bee Wee, Sir Michael Sobell House, Oxford; Mary O'Brien, Royal Marsden Hospital; Patrick Stone, St George's University of London; Tim Benepal, St George's Hospital NHS Trust, London; and Nick Bates, Buckinghamshire Healthcare NHS Trust, Aylesbury, United Kingdom.
Bee
B
Wee
D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications*; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D000077408:Modafinil; D015990:Placebo Effect; D012720:Severity of Illness Index; D017211:Treatment Failure; D006113:United Kingdom; D064690:Wakefulness-Promoting Agents / Q000627:therapeutic use
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D064690:Wakefulness-Promoting Agents; D008774:Methylphenidate; D000077408:Modafinil