Modafinil controlled severe cancer-related fatigue

CHICAGO — There may be a new treatment option for the 70% to 100% of cancer patients who experience cancer-related fatigue during and after treatment: the eugeroic agent modafinil.

“A majority of cancer patients expect to be fatigued and unfortunately they are right,” Gary R. Morrow, PhD, of the radiation oncology department at the University of Rochester, N.Y., said during a press briefing at the 2008 ASCO Annual Meeting. “Modafinil appears to be useful to treat severe fatigue.”

As part of the University of Rochester Cancer Center Community Clinical Oncology Program, Morrow and colleagues conducted a randomized, placebo-controlled, double blind trial comparing modafinil and placebo in the treatment of cancer-related fatigue.

Six-hundred forty-two patients were randomly assigned to receive 200 mg of modafinil orally (n=320) or placebo (n=322) if they scaled their fatigue greater than one on a one to 10 fatigue scale. Mild fatigue was scored zero to four; moderate, five to six; and severe, seven to 10. Fatigue was assessed at baseline and after cycles two and four of chemotherapy.

Patients assigned modafinil with severe cancer-related fatigue demonstrated a significant improvement compared with placebo (P=.017). Patients whose fatigue was classified as mild or moderate at baseline did not. Modafinil had no effect on depression (P=.83).

Morrow GR. #9512. Presented at: 2008 ASCO Annual Meeting; May 30-June 2, 2008; Chicago.

Modafinil is a psycho-stimulant used to treat excessive sleepiness associated with various sleep disorders. This randomized control trial reports that a subgroup of patients with severe fatigue undergoing chemotherapy in outpatient setting had improvement in their sleepiness with modafinil. This may be hypothesis-generating finding as it is unclear whether the study has adequate power to detect improvement for the subgroup. This study also points out the difficulty in the treatment of fatigue. We still do not know what causes fatigue and how it interacts with other symptoms such as depression. Another trial by the same research group has previously reported that depressive symptoms improved with paroxetine, but not fatigue. Those patients with severe fatigue and excessive sleepiness may benefit from this drug. Caution should be used in patients who develop rash during this therapy as in rare cases it can progress to Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis.

- Biren Saraiya, MD

Cancer Institute of New Jersey at UMDNJ-Robert Wood Johnson Medical School