Fatigue (PDQ®): Supportive care - Health Professional Information [NCI] - Intervention
The one study that demonstrated significant improvements over placebo for CRF used a mean dose of 27.7 mg of the D-isomer of methylphenidate as a study intervention. The population that benefited was women who had completed chemotherapy for breast or ovarian cancer. The study design incorporated a titration to effect, so some patients who may have benefited may have received more than 27.7 mg of the drug. Furthermore, 11% of participants on this trial withdrew because of adverse events, compared with 1% in the placebo arm. Conversely, an equally large randomized controlled trial randomly assigned patients with early and advanced disease, both on and off treatment, to receive 54 mg of a long-acting methylphenidate preparation equaling 27 mg of the D-isomer or a placebo; this trial found no differences between the two groups in any of the fatigue outcomes.[Level of evidence: I] There were significant differences between groups for nervousness and appetite loss, with the methylphenidate arm scoring worse on both of those side effects.
The newer so-called wake-promoting agents, modafinil and armodafinil, are just beginning to be studied for CRF. Modafinil is a centrally acting, nonamphetamine, central nervous system stimulant. Armodafinil is the R-enantiomer of modafinil and an alpha-1 adrenoceptor agonist. Modafinil and armodafinil are approved by the FDA for narcolepsy, obstructive sleep apnea, and shift-work disorders. Neither of these agents is approved by the FDA for the treatment of CRF. These agents are also not indicated for use in children and adolescents. The mechanism of action of modafinil and armodafinil is different from that of amphetamines, but the exact mechanisms by which these agents improve wakefulness are not known. On the basis of a couple of promising open-label pilot trials,[11,12] a large randomized controlled trial evaluated modafinil for CRF using 200 mg versus placebo in more than 850 patients receiving chemotherapy. Patients had to have fatigue ratings of at least 2 out of 10 to be eligible for this study. During four cycles of chemotherapy, this study failed to show significant differences between arms. Because armodafinil is newer to the marketplace, research on its possible role in CRF has not yet been published. More research is needed to identify whether modafinil and armodafinil can ameliorate fatigue and which populations of cancer survivors can benefit most from them.