‘Insufficient Evidence’ for Fatigue Drug in Cancer Patients

Modafinil shows a significant placebo effect on fatigue symptoms in patients with advanced lung cancer

medwireNews: The vigilance promoting drug modafinil should not be used for the treatment of cancer-related fatigue, UK researchers advise on finding placebo to be equally effective.

The team, led by Anna Spathis, from Addenbrookes Hospital in Cambridge, found comparable improvement of fatigue symptoms in the 75 patients with advanced non-small-cell lung cancer (NSCLC) who were randomly assigned to receive double-blind modafinil and the 85 patients given placebo.

After 28 days of treatment, Functional Assessment of Chronic Illness therapy (FACIT)–Fatigue scores had significantly improved from baseline by an average of 5.29 points for modafinil-treated patients. But this gain did not significantly differ from the mean 5.09-point increase in FACIT–Fatigue scores achieved by controls.

And although both the modafinil and placebo treatment groups reported improvements in daytime sleepiness, neither group experienced significant improvements with regard to anxiety, depression or quality of life.

Furthermore, 47% of the modafinil-treated patients and 23% of controls said their treatment was “not helpful” and modafinil-treated patients were significantly more likely to withdraw from treatment than controls (30 vs 16).

The modafinil and placebo treatment groups had comparable rates of adverse events (55.8 vs 54.4%) but serious events potentially related to treatment were more common in the modafinil than placebo group (n=4 vs 2).

Noting their results mirror an earlier trial reporting negative results for modafinil in patients undergoing chemotherapy for breast, gastrointestinal or lung cancer, the team writes: “There is insufficient evidence to prescribe modafinil for patients with cancer-related fatigue outside of a clinical trial context.”

Nevertheless, the researchers emphasise that the “clinically significant placebo effect found in this trial is, in itself, an important finding.”

They say: “Further research is needed to identify the precise component of being involved in a clinical trial and taking a placebo drug that improves this subjective symptom.”

Anna Spathis and co-authors conclude in the Journal of Clinical Oncology: “Cancer-related fatigue is relatively neglected, beset by therapeutic nihilism on the part of both clinicians and patients.

“Simply allocating the time within a clinical consultation to acknowledge and discuss fatigue may benefit the many patients experiencing this distressing symptom.”


Spathis A, Fife K, Blackhall F, et al. Modafinil for the treatment of fatigue in lung cancer: Results of a placebo-controlled, double-blind, randomized trial. J Clin Oncol 2014; Published online before print 28 April. Doi: 10.1200/JCO.2013.54.4346

medwireNews (www.medwireNews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2014