Become an AAHPM Member to view PC-FACS
Design and Participants: This study examined the efficacy and safety of temazepam or melatonin vs placebo for sleep in advanced cancer. Adult patients with incurable solid or hematological malignancy of any etiology with an insomnia severity index (ISI) score greater than 11, an Australia-modified Karnofsky Performance Status score of 40 or more, and predicted survival more than 2 weeks were randomized (2:2:1) to receive temazepam (starting 10 mg), melatonin PR (2 mg), or placebo using permuted block randomization (stratified by site using an independent randomization list). Participants took the medication 7 consecutive days, 30 minutes before usual bedtime. Assessments occurred at baseline, day 3, and day 8. If ISI score on day 3 was not four or more points below baseline, the dose was doubled from day 4. Outcomes were patient-reported sleep quality (ISI; 0-28, higher scores indicating worse insomnia and ≥15 indicating moderate to severe) on day 8, quality of life (EORTC Quality of Life in Palliative Cancer Care Patients questionnaire), tolerability (Karolinska Sleepiness Scale score within 2 hrs of waking), falls, and hospital admissions for delirium. Linear regression was used.
Results: Participants (n=9 temazepam, n=8 melatonin, n=4 placebo) were aged mean 59 yrs (SD=12) and 60% male; 55% were receiving systemic treatment. The adjusted mean difference in day 8 ISI score vs placebo was −9.1 (95% CI=−18-−0.7) for temazepam and −9.6 (−18-−1.2) for melatonin. There was no improvement in global quality of life. Both agents were well tolerated.
Commentary: This randomized trial addresses the evidence gap for pharmacological treatment of insomnia in adults with advanced cancer, and reports improvement in insomnia with temazepam or melatonin. A major study limitation is the small sample size due to recruitment being hindered by the COVID-19 pandemic, stigma of sleep medications being addictive, concern for drug-drug interactions with opioids, and difficulty recruiting participants not receiving sleep aids. Notably, more than two-thirds of participants were receiving opioids, yet dose escalations of temazepam (44%) and melatonin (12%) did not demonstrate increased risks of falls or hospitalizations for delirium and is reassuring for short-term use of these medications. However, patients in both treatment arms were younger than the placebo group, limiting generalizability of safety data, especially the use of benzodiazepines in older patients.
Bottom Line: Pharmacological treatment of insomnia with temazepam or melatonin shows promise for patients with advanced cancer, yet more research is needed with attention to safety during long-term use, especially in older adults.
Reviewer: Christopher D. Woodrell, MD MS FAAHPM, Icahn School of Medicine at Mount Sinai, New York, NY, and James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY
References:
1. Mercadante S, Adile C, Ferrera P, et al. Sleep disturbances in advanced cancer patients admitted to a supportive/palliative care unit. Support Care Cancer. 2017;25(4):1301-1306.
2. Mercadante S, Aielli F, Adile C, et al. Sleep disturbances in patients with advanced cancer in different palliative care settings. J Pain Symptom Manage. 2015;50(6):786-792.
3. Krause AJ, Prather AA, Wager TD, et al. The pain of sleep loss: a brain characterization in humans. J Neurosci. 2019;39(12):2291-2300.
Source: Mendis R, Wong A, Frenkel S, et al. Temazepam or melatonin versus placebo for the treatment of insomnia in advanced cancer: a three-arm, double-blind, Phase III, multicenter, randomized clinical trial. J Palliat Med. 2024;27(10):1368-1373. doi:10.1089/jpm.2024.0151.
Access this article on PubMed.