No rest for fatigue researchers.

F atigue is the most important side effect of cancer and cancer treatment, according to a recent study of patients and professionals in major cancer centers across the United States. Led by David Cella, Ph.D., at Evanston Northwestern Healthcare and Northwestern University's cancer center in Chicago, the study confirms not only that cancer-related fatigue is common but also that it affects patients with diverse cancers. Patients undergoing treatment for nine different kinds of advanced cancer ranked it as their most important symptom or concern; patients with two other kinds of cancer ranked it among their top five concerns. Unfortunately, fatigue is still harder to treat than other common, cancer-related symptoms such as pain and nausea. of London and colleagues report their fi ndings from a systematic review and meta-analysis of drugs targeted at cancer-related fatigue. Limiting their review to randomized controlled cancer trials that focused on cancer-related fatigue, they identifi ed three drugs with some evidence of effectiveness. But each of the three has important limitations. Methylphenidate (Ritalin), a psy-chostimulant, has been tested in only two small trials of cancer-related fatigue (most trials of the drug have focused on chronic fatigue syndrome rather than cancer-related fatigue). Also, methylphenidate is a controlled drug and has side effects, including addiction, that limit its usefulness. The second drug, darbepoetin alfa (Aranesp), showed only borderline superiority over placebo among anemic patients participating in four cancer trials included in the review. The third drug, epoetin alfa (Procrit and Epogen), has evidence of effectiveness in patients with chemotherapy-induced anemia but, like darbepoetin, has not been shown to affect fatigue in nonanemic cancer patients. In fact, a public health advisory from the U.S. Food and Drug Administration, issued in March, warns that these erythropoiesis-stimulating agents have not been approved for cancer-related fatigue in nonanemic patients. The advisory was issued in the wake of recent studies showing that such drugs increase mortality and tumor progression rates in head and neck and breast cancer, as well as increasing cardiovascular risks among cancer patients and others. Another drug, modafi nil (Provigil), had some effect on severe fatigue in a random-ized controlled trial reported at the annual meeting of the American Society for Clinical Oncology in June. But the drug,