A large, phase III clinical study showed the drug modafinil (Provigil) alleviated severe cancer-related fatigue for many patients, paving the way for the first reliable treatment for this debilitating and common side effect.
The American Society of Clinical Oncology (ASCO) invited principle investigator Gary R. Morrow, Ph.D., M.S., director of the University of Rochester Cancer Center Community Clinical Oncology Research Base (URCC CCOP) to present the study June 2 at the ASCO annual meeting in Chicago, taking place from May 30 to June 3, 2008.
The randomized trial included 642 patients who were receiving chemotherapy for a variety of cancers. Investigators asked them to complete a survey twice assessing their level of fatigue, sleepiness and depression. The initial survey was conducted at the second cycle of chemotherapy and a follow-up survey was taken during the fourth cycle of chemotherapy.
A standard scale, similar to the one used to measure pain, asked patients to rate their level of fatigue from zero ("none") to 10 ("as bad as it can be"). Anyone who reported a fatigue value greater than two was randomly assigned to receive either 200 mg daily of modafinil or an identical looking placebo pill. There were 320 people in the modafinil group and 322 in the placebo group.
Researchers found that the patients who had the most severe fatigue at the beginning of the study showed the most significant improvement after taking the drug, while patients with mild or moderate fatigue showed no significant improvement. Modafinil also improved sleepiness, but not depression, compared to the placebo group.
"Although this drug did not have a positive effect for everyone, until now there was nothing reliable to prescribe for people who are most severely fatigued," said Morrow, a professor of Radiation Oncology and Psychiatry, and a researcher at the James P. Wilmot Cancer Center at the University of Rochester Medical Center.
Eugeroic agents such as modafinil promote wakefulness without interfering with sleep or causing addiction concerns because they clear from the body in about 12 hours. The U.S. Food and Drug Administration has approved modafinil for the treatment of narcolepsy, sleep apnea and other sleep-related disorders. The University of Rochester Medical Center has also tested modafinil to treat chemo-brain, a cognitive disorder resulting from chemotherapy.
Managing cancer-related fatigue is important, as patients seek to go on with their lives during treatment. The scientific literature shows that 95 percent of cancer patients expect to be fatigued during treatment - and they are, Morrow said.
In previous studies, Morrow and his group have shown that 80 to 85 percent of people receiving chemotherapy report fatigue and nine of 10 radiation patients report it.
Researchers do not yet understand why modafinil appears to work best in the most severely fatigued patients. But Morrow said the benefits simply might be more evident in that group.
"If you think about it in the context of severe nausea or a pounding headache - any amount of relief is going to be noticeable," Morrow said.
Another interesting aspect of the study, Morrow said, was that modafinil appeared to have no impact on depression, which is often linked to fatigue.
"Our data show that fatigue and depression are very different," Morrow said. "We've also tested anti-depressants such as Paxil with cancer patients and as expected, it helped their depression - but it did nothing for fatigue."
The National Cancer Institute funded the research. Cephalon Inc., the manufacturer of Provigil, provided the drug samples and placebo.