St. Jude finds anti-leukemia drug increases patient fatigue

The anti-leukemia drug dexamethasone contributes to a relentless fatigue and poor quality of sleep in children undergoing treatment for acute lymphoblastic leukemia (ALL), according to a new study from St. Jude Children's Research Hospital. The finding suggests that clinicians could improve the quality of life for these children by developing new methods of drug administration that reduce or eliminate these side effects.

The St. Jude team showed that dexamethasone significantly increased patients?fatigue, length of daytime naps, frequency of awakening at night and the amount of restlessness during sleep. The findings also suggest that before initiation of continuation therapy for ALL, health care workers should prepare patients and families to expect an increase in disrupted sleep and fatigue during dexamethasone treatment. Continuation therapy is the long-term treatment that occurs following the initial intensive use of anti-cancer drugs designed to quickly reduce the number of cancer cells.

“Parents and patients have long reported altered behaviors during dexamethasone treatment, but this is the first trial to document that disrupted sleep and fatigue are behavioral indicators of patients?response to the treatment,?said Pamela Hinds, Ph.D., R.N., director of the Division of Nursing Research at St. Jude. Hinds is the first author of this study, which appears in the online version of the journal “Cancer.?

Previous studies had found that dexamethasone was especially effective in the treatment of ALL, but that it could also cause a variety of side effects in children, including fatigue. Therefore, the St. Jude team designed the current study to determine if the direct and consistent link between dexamenthasone and fatigue and disrupted sleep in children was significant and common.

“Before we could begin to revise the way we give dexamethasone to children we had to establish if the drug routinely disrupts the sleep of children, or whether it’s only an occasional problem among specific children,?Hinds said. “We found that it’s a widespread problem across all age groups.?The study included 100 pediatric patients, with an average age of nine years, who were treated at St. Jude, Texas Children’s Cancer Center in Houston and Hospital for Sick Children in Toronto.

Researchers monitored the sleep activity of children during two consecutive five-day periods by having them wear a wristwatch-style device called an actigraph, which senses motion and stores the information on a computer chip. The children did not receive dexamethasone during the first five-day period, but were treated with the drug during the second period. In addition, parents kept a “sleep diary,?in which they recorded their daily perceptions of their child’s sleep and nap patterns during the previous 24-hour period. Children, ages 7 to 12 years, and adolescents, ages 13 to 18, completed surveys, rating how tired they were; and parents filled out surveys about their perception of their child’s fatigue.

“Now that we have demonstrated that dexamethasone is so disruptive of sleep and causes profound fatigue in children with ALL, we will study ways to reduce these troublesome side effects, while still allowing the patients to get full benefit of the treatment,?said Ching-Hon Pui, M.D., chair of the St. Jude Department of Oncology and the paper’s senior author. “This would help us continue to improve the already high quality of care we provide to children with ALL.?