Modafinil for the Treatment of Fatigue in Lung Cancer: Results of a Placebo-Controlled, Double-Blind, Randomized Trial

1. Anna Spathis⇑,
2. Kate Fife,
3. Fiona Blackhall,
4. Susan Dutton,
5. Ronja Bahadori,
6. Rose Wharton,
7. Mary O’Brien,
8. Patrick Stone,
9. Tim Benepal,
10. Nick Bates and
11. Bee Wee

+ Author Affiliations

1. 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.

1. Corresponding author: Anna Spathis, MSc, Consultant in Palliative Medicine, Addenbrookes Hospital, Cambridge, United Kingdom CB2 0QQ; e-mail: aspathis@doctors.org.uk.

Abstract

Purpose 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).

Patients and 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.

Conclusion 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.