Table 1

The characteristics of the literature

AuthorYearPopulationMean age
(intervention/ control）		Study designTime of durationAdministration timeIntervention groupControl groupOutcomeIntervention
(N)		Control
(N)
Lissoni et al311997Patients with metastatic solid tumours under chemotherapy61/58RCTsEvery day without a break until disease progressionEvery night20 mg oral MLTPlaceboStomatitis rate3940
Lissoni et al301999Patients with metastatic solid tumour under chemotherapy53/56RCTs7 days prior to chemotherapy, continued after chemotherapy interruption, until disease progressionEvery night20 mg oral MLTPlaceboStomatitis rate124126
Lissoni et al292002Untreated patients with metastatic solid tumours under chemotherapy66/65RCTsAt least 2 monthsEvery night20 mg oral MLT plus support carePlacebo plus support careStomatitis rate98102
Hansen et al272014Patients undergoing breast cancer surgery51/60RCTs10days: 2 days preoperatively till 8 days postoperativelyOne hour before bedtime6 mg oral MLTPlaceboDepression (MDI), Sleepiness (KSS, VAS), Fatigue (VAS), Pain (VAS)2826
Chen et al242014Breast cancer survivors59/59RCTs4 monthsEach night at nine pm3 mg oral MLTPlaceboSleep (PSQI), depression (CES-D)4847
Sookprasert et al412014Patients with non-small cell lung cancer receiving chemotherapy56.8/55.6RCTs2 months: during chemotherapyAt night after 21:0010 mg or 20 mg oral MLTPlaceboQOL(FACT-L), Mucositis rate8838
Lund Rasmussen et al332015Patients with advanced cancer who reported significantly tired in palliative care unit64/65RCTs7 daysEvery night20 mg oral MLTPlaceboFatigue (MFI-20), QOL (EORTC QLQ-C15-PAL), Insomnia (EORTC QLQ-C15-PAL)2123
Madsen et al342016Patients undergoing breast cancer surgery51/59RCTs2 weeks: 3 days preoperatively until 2 weeks postoperativelyOne hour before bedtime6 mg oral MLTPlaceboSleep (VAS, KSS), pain (VAS)2721
Kurdi et al282016Patients with cancer with Insomnia55.2/49.64RCTs14 daysAt 19:00 hours3 mg oral MLTPlaceboSleep (AIS)2525
Onseng et al352017Patients with head and neck cancer receiving concurrent chemoradiation47.3/49.6RCTs35days: 5 days a week throughout the 7 weeks of chemoradiationAt night after 21:0010 mL of a 0.2% MLT niosome oral gargle plus 20 mg oral dosageplaceboQOL (FACT—H&N), Mucositis rate, Mucositis severity (WHO-G)1920
Elsabagh et al252019Patients with head and neck cancer undergoing radiotherapy57.8/55.9RCTsSix weeks30 min before sleeping20 mg oral MLTPlaceboStomatitis severity (WHO-G), Stomatitis rate, Pain (NRS)2020
Palmer et al362019Patients with breast cancer receiving chemotherapy54.24/54.11RCTs10 days during treatment.One hour before bedtime20 mg oral MLTPlaceboPain (NRS), Sleep (PSQI), Depression (BDI)1818
Yennurajalingam et al422019Patients with advanced cancer with poor sleep qualityNot clearlyRCTs14 daysAt bedtime20 mg oral MLT plus bright white light therapyBright white light therapy aloneSleep (PSQI), insomnia (ISI), fatigue (FACIT-F), depression (HADS), QOL(FACT)68
Palmer et al372020Patients with breast cancer undergoing chemotherapy after lumpectomy or mastectomy54.24/54.11RCTs10 days: 3 days prior to chemotherapy and seven following daysOne hour before bedtime20 mg oral MLTPlaceboDepressive symptoms (BDI-II), Sleep quality (PSQI), QOL (EORTC QLQ-C30)1818
Sedighi Pashaki et al382021Patients with breast cancer during adjuvant chemotherapy and radiotherapy50.47/46.05RCTs8 weeks: from 1 week before until 1 month after the adjuvant radiotherapyOne hour before bedtime18 mg oral MLTPlaceboFatigue (BFI)3836
Seely et al392021Patients with cancer following lung cancer resection67.2/67.2RCTsOne year after surgeryOne hour before bedtime20 mg oral MLTPlaceboFatigue (MFI-20), QOL(QLQ-LC13), Sleep (MOS), Depression (BDI 2), Pain (BPI)356353
Shahrokhi et al402021Patients with colorectal cancer undergoing chemotherapy with sleep disorder63.63/64.11RCTs4 weeks of treatmentAt bedtime6 mg oral MLT10 mg zolpidemSleep (GSQS, PSQI), Depression (HRSD)4545
Grutsch et al262021NSCLC patients under chemotherapy60.3/63RCTsFrom intervention to deathAt 8:00 hours or at 20:00 hours20 mg oral MLTPlaceboQOL(QLQ-C30), Fatigue (QLQ-C30), Pain (QLQ-C30), Sleep (PSQI)2018
A. Lozano et al322021Patients with head and neck cancer undergoing radiation therapy and chemical treatment59/56RCTs5 days a week, lasting 7 weeksNot clearly3% oral MLT gel plus standard symptomatic treatment for stomatitisPlacebo plus standard symptomatic treatment for stomatitisStomatitis severity (WHO-G), Stomatitis rate4039

  • . AIS, Athens insomnia scale; BDI 2, Beck Depression Inventory 2; BDI-II, Beck Depression Inventory; BFI, Brief Fatigue Inventory; BPI, Brief Pain Inventory; CES-D, Center for Epidemiologic Studies-Depression; EORTC QLQ-C30, European Organisation for Cancer Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ-C15-PAL, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Version; FACIT-F, Functional Assessment of Cancer Illness Therapy-Fatigue subscale; FACT, Functional Assessment of Cancer Illness Therapy; FACT-H&N, Functional Assessment of Cancer Therapy-H&N Version 4; FACT-L, Functional Assessment of Cancer Therapy-Lung; GSQS, Sleep Quality Scale; HADS, Hospital Anxiety and Depression Scale; HRSD, Hamilton Rating Scale for Depression; ISI, Insomnia Severity Index; KSS, Karolinska Sleepiness Scale; MDI, Major Depression Inventory; MFI-20, Multidimensional Fatigue Inventory; MLT, Melatonin; MOS, Medical Outcomes Study Sleep Survey; N, number; NRS, Numeric Rating Scales; PSQI, Pittsburgh Sleep Quality Index; QLQ-LC13, Lung Cancer-13 modules; RCTs, randomised controlled trials; VAS, Visual Analogue Scale; WHO-G, WHO grading system.