Modafinil appears to alleviate chemotherapy-induced fatigue

Modafinil appears to reduce the severity of chemotherapy-induced severe fatigue, reported Gary R. Morrow, PhD, MS, at the 2008 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Ninety-five percent of patients about to undergo chemotherapy expect fatigue as one of the side effects. The actual incidence of fatigue with chemotherapy is about 80%, said Dr. Morrow, associate director for community research, University of Rochester Cancer Center, Rochester, NY.

Some 30% to 40% of cancer survivors report debilitating fatigue several years beyond completion of therapy. "Despite speculation, we don't have a clue as to what causes it," he said.

Previous open-label studies had suggested that the eugeroic agent modafinil, a drug with stimulatory properties and no peripheral effects without the potential for abuse or addiction, was promising for treating cancer-related fatigue.

In the placebo-controlled, randomized, double-blind study that Dr. Morrow presented, 631 cancer patients being treated with chemotherapy who reported a fatigue score of 1 or greater on a 10-point fatigue scale were randomized to modafinil, 200 mg/day, or placebo. The treatment began on the fifth day of chemotherapy cycle 2 and ended after the seventh day of cycle 4. The baseline fatigue score was assessed after cycle 2.

In the overall cohort at cycle 4, modafinil was associated with a significant (p = 0.03) reduction in fatigue from baseline compared with placebo. The strength of the effect of modafinil on fatigue was dependent on fatigue severity at baseline, said Dr. Morrow.

In patients who reported mild or moderate fatigue at baseline, there were nonsignificant trends toward a reduction in fatigue from baseline compared with placebo in patients who were randomized to modafinil. In patients who reported severe fatigue (> 6 on the 10-point fatigue scale) at cycle 2, modafinil was significantly better than placebo (p = 0.034) on the change in fatigue score from baseline.

Modafinil had no effect on depression scores in this study.