Trial findings indicate melatonin may be a potentially effective solution for reducing the incidence and severity of cancer-related fatigue among patients with breast cancer.
Long-term treatment with melatonin appeared to reduce disease-related fatigue in a cohort of patients with breast cancer even after the conclusion of adjuvant therapy, according to findings from a clinical trial conducted in Iran and published recently in Integrative Cancer Therapies.
Melatonin treatment yielded a mean fatigue score of 3.97±1.29, whereas placebo yielded a score of 4.80±1.02 after 1 month of treatment (P = .007). Moreover, at this time point, 16 patients in the melatonin group reported severe fatigue compared with 29 in the placebo group (P = .029). Mean severity scores were 3.66±1.20 vs 4.76±1.27 in the melatonin and placebo groups, respectively (P <.001).
These tendencies were constant after 2 years, with a mean fatigue score of 1.97±1.08 in the melatonin group vs 2.94±1.03 in the placebo group (P <.001). Additionally, 6 patients in the melatonin group reported severe fatigue vs 13 in the placebo group (P = .096). The mean severity score was 1.99±1.02 with melatonin vs 2.93±1.04 with placebo (P <.001).
Overall, the melatonin group experienced a greater reduction in fatigue score over time (P ≤.001).
“Our findings support using melatonin as an effective therapeutic method for improving cancer-related fatigue in breast cancer survivors in patients who can tolerate the melatonin-induced nausea that might have been considerable if prescribed during the chemotherapy in a portion of patients,” the investigators wrote.
“There is possibility that a decrease in [cancer-related fatigue] is associated with an increase in [quality of life] as well as a decrease in the distress caused by symptoms, including pain, poor appetite, feeling drowsy, bowel problems, xerostomia, nausea, vomiting, losing weight, and feeling dizzy. More research is needed into this potential association.”
Investigators of this double-blind, randomizedtrialenrolled 208 patients in 2019 and 2020, of whom 102 were assigned to the melatonin group and 106 were assigned to placebo. In the former group, 6 patients were then excluded due to severe nausea and vomiting, and 5 were excluded due to distant metastases or recurrence. In the latter group, 6 patients were excluded due to failure to follow up and 8 due to distant metastases or recurrence. The last follow-up date was June 2022.
Investigators employed the Persian version of the Brief Fatigue Inventory to assess cancer-related fatigue in the study population.
All patients had an ECOG performance status of 0 or 1, and received conventional rather than hypofractionated radiotherapy. Most patients in both groups underwent breast-conserving surgery rather than modified radical mastectomy, and most had received doxorubicin-based chemotherapy. Most patients had also received tamoxifen.
Patients in the intervention group received oral melatonin at a dose of 18 mg daily every night 1 hour before sleeping, beginning 1 week prior to adjuvant treatment and concluding 2 years after completion of adjuvant radiotherapy. Those in the control group received a similar cellulose-made drug on the same schedule.
The occurrence of any grade 2 or higher toxicities during the treatment led to exclusion from the study. Other exclusion criteria included a prior history of any other malignancies aside from cutaneous basal cell carcinoma, receipt of previous chemotherapy, evidence of distant metastasis at presentation, and receipt of neoadjuvant chemotherapy.
The social and financial status of the enrolled patients may have impacted fatigue scores, which investigators were unable to control for; this was one noted potential limitation to the study. Patients’ primary serum melatonin levels, which may have impacted the efficacy of the treatment, were also not evaluated.
“According to our search, no other study evaluated the long-term prescription of melatonin in patients [with breast cancer],” the investigators concluded. “Given the long-term [adverse] effects of breast cancer and its treatments, large-scale randomized controlled trials might be advantageous to determine the effects of this intervention on the level of fatigue, quality of life, and, potentially, survival of long-term breast cancer survivors.”
Pashaki AS, Sheida F, Shoar LM, et al. A randomized, controlled, parallel-group, trial on the long-term effects of melatonin on fatigue associated with breast cancer and its adjuvant treatments. Integr Cancer Ther. Published online May 4, 2023. doi:10.1177/15347354231168624