A phase 3 randomized, placebo-controlled, double-blind, clinical trial of the effect of modafinil on cancer-related fatigue among 631 patients receiving chemotherapy: a University of Rochester Cancer Center Community Clinical Oncology Program Research base study.

Background: Cancer-related fatigue is a debilitating symptom affecting psychosocial functioning and quality of life in 70% to 100% of cancer patients during and after treatment. The authors examined the effect of 200 mg of modafinil daily on the severity of cancer-related fatigue.

Methods: The authors conducted a multicenter, randomized, double-blind, placebo-controlled, phase 3, clinical trial to examine the effect of modafinil on patient-reported fatigue in cancer patients undergoing chemotherapy. A sample of 877 cancer patients beginning chemotherapy at 23 geographically separate University of Rochester Cancer Center (URCC) Community Clinical Oncology Program (CCOP) affiliates were assessed for fatigue. Patients who reported fatigue (N=867) were randomly assigned to receive either 200 mg of oral modafinil (Provigil) daily or a placebo. Treatment began on Day 5 of Cycle 2 and ended after Day 7 of Cycle 4. Fatigue and depression were assessed during Cycles 2 to 4 by using psychometrically valid measures. Group differences (treatment vs control) in the worst level of fatigue during the previous week at Cycle 4 were examined by using an analysis of covariance (ANCOVA) adjusting for baseline fatigue (Cycle 2).

Results: There were 631 patients (315 modafinil, 316 placebo) who provided evaluable data. ANCOVA showed a significant interaction between treatment condition and baseline fatigue (P=.017), where patients with severe baseline fatigue (n=458) benefited from modafinil, whereas patients with mild or moderate fatigue did not. Modafinil had no statistically significant effect on depression (P>.05).

Conclusions: Modafinil may be useful in controlling cancer-related fatigue in patients who present with severe fatigue but is not useful in patients with mild or moderate fatigue.