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Relation
Hrushesky WJM, Lis CG, Levin RD, et al. Daily evening melatonin prolongs survival in patients with advanced non-small cell lung cancer.Biol Rhythm Res.2021:1-15. DOI: 10.1080/09291016.2021.1899485.
Study objective
To evaluate the survival benefit of melatonin in patients with advanced non-small cell lung cancer (NSCLC) when given at different times of the day compared to placebo
Draft
A placebo-controlled, randomized, double-blind, 3-arm clinical trial
Participant
84 patients with advanced (stage IIIB or IV) NSCLC between the ages of 18 and 80 years who received identical doses of standard etoposide/cisplatin therapy.
Inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
intervention
Patients were randomly assigned to 1 of 3 arms:
- Placebo um 8 Uhr und 20 Uhr
- 20 mg Melatonin um 8 Uhr morgens und Placebo um 20 Uhr
- Placebo um 8 Uhr morgens und 20 mg Melatonin um 20 Uhr
Study parameters assessed
The researchers used a Kaplan-Meier survival chart to track median survival for each of the groups.
They assessed quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the Ferrans and Powers Quality of Life Index (QLI).
Researchers also collected and measured sleep quality data using the Pittsburgh Sleep Quality Index (PSQI).
Primary outcome measures
The most important outcome parameters were overall survival and sleep quality. Secondary endpoints were objective tumor response and quality of life.
Key insights
In the nighttime melatonin group, there was a statistically significant (P=0.031) reduced the risk ratio for overall survival by 39% compared to the placebo group. The placebo group had a median survival of 10.4 months, while the nighttime melatonin group had a median survival of 17.6 months.
Sleep quality and sleep efficiency had a statistically significant impact on survival, and improvement in sleep quality from baseline resulted in an even greater decrease in overall survival hazard ratio.
Notably, sleep efficiency had a negative impact on the hazard ratio, although this is likely due to patients spending more time resting rather than open sleep due to illness.
There was no group with notable tumor response, and unfortunately there were no patients who demonstrated a complete response; However, the most common response was stable disease, and this prevalence was higher in the evening melatonin group.
Practice implications
Sleep is a wonderful thing for our bodies and our brains. It has been proven that adequate sleep is essential for overall health. Sleep also has numerous benefits for risk reduction in a range of cancers and plays a critical role in the tolerability of chemotherapy and radiation treatment for our oncology patients. At the beginning of my residency training, I came across a study that described how our bodies secrete anti-inflammatory cytokines while we sleep. I realized that melatonin has a major impact specifically on nuclear factor kappa B (NF-κB), which is considered the emperor of the inflammatory cascade.1This helps to explain why generalized inflammatory symptoms such as joint pain,2Swelling, fatigue, headaches, anxiety/depression, or an upset digestive system are often milder upon waking in the morning than before bed.
This helps explain why common inflammatory symptoms such as joint pain, swelling, fatigue, headaches, anxiety/depression, or an upset digestive system are often milder upon waking in the morning than before bed
A recent study describes how shift workers can have elevated levels of inflammation, which can lead to immune system dysregulation and the many adverse consequences of shift work, with cancer likely being one of them.3.4Melatonin is an anti-inflammatory compound and an immune system modulating hormone.5It's not surprising that melatonin can help normalize circadian rhythms and improve outcomes for cancer patients.6
In addition to improving quality of life through better sleep, melatonin influences multiple intracellular signaling pathways that lead to downregulation of growth and increased chemosensitivity in non-small cell lung cancer patients receiving chemotherapy.7.8
This particular study focused on the importance of timing melatonin and found a significant survival benefit for patients with advanced lung cancer who took melatonin in the evening. This benefit was not found in those who took melatonin in the morning. This study suggests that nighttime dosing of melatonin is a critical part of this hormone's value.
Melatonin is inexpensive and well tolerated by the vast majority of patients. With trial data accumulating suggesting benefits for sleep, bone marrow recovery, and overall survival during conventional treatment, I'm starting to wonder what melatonin doesnotdo for our patients with non-small cell lung cancer?