. 2022 Sep 14;12(9):e060912. doi: 10.1136/bmjopen-2022-060912

Table 1.

The characteristics of the literature

Author	Year	Population	Mean age (intervention/ control）	Study design	Time of duration	Administration time	Intervention group	Control group	Outcome	Intervention (N)	Control (N)
Lissoni et al³¹	1997	Patients with metastatic solid tumours under chemotherapy	61/58	RCTs	Every day without a break until disease progression	Every night	20 mg oral MLT	Placebo	Stomatitis rate	39	40
Lissoni et al³⁰	1999	Patients with metastatic solid tumour under chemotherapy	53/56	RCTs	7 days prior to chemotherapy, continued after chemotherapy interruption, until disease progression	Every night	20 mg oral MLT	Placebo	Stomatitis rate	124	126
Lissoni et al²⁹	2002	Untreated patients with metastatic solid tumours under chemotherapy	66/65	RCTs	At least 2 months	Every night	20 mg oral MLT plus support care	Placebo plus support care	Stomatitis rate	98	102
Hansen et al²⁷	2014	Patients undergoing breast cancer surgery	51/60	RCTs	10days: 2 days preoperatively till 8 days postoperatively	One hour before bedtime	6 mg oral MLT	Placebo	Depression (MDI), Sleepiness (KSS, VAS), Fatigue (VAS), Pain (VAS)	28	26
Chen et al²⁴	2014	Breast cancer survivors	59/59	RCTs	4 months	Each night at nine pm	3 mg oral MLT	Placebo	Sleep (PSQI), depression (CES-D)	48	47
Sookprasert et al⁴¹	2014	Patients with non-small cell lung cancer receiving chemotherapy	56.8/55.6	RCTs	2 months: during chemotherapy	At night after 21:00	10 mg or 20 mg oral MLT	Placebo	QOL(FACT-L), Mucositis rate	88	38
Lund Rasmussen et al³³	2015	Patients with advanced cancer who reported significantly tired in palliative care unit	64/65	RCTs	7 days	Every night	20 mg oral MLT	Placebo	Fatigue (MFI-20), QOL (EORTC QLQ-C15-PAL), Insomnia (EORTC QLQ-C15-PAL)	21	23
Madsen et al³⁴	2016	Patients undergoing breast cancer surgery	51/59	RCTs	2 weeks: 3 days preoperatively until 2 weeks postoperatively	One hour before bedtime	6 mg oral MLT	Placebo	Sleep (VAS, KSS), pain (VAS)	27	21
Kurdi et al²⁸	2016	Patients with cancer with Insomnia	55.2/49.64	RCTs	14 days	At 19:00 hours	3 mg oral MLT	Placebo	Sleep (AIS)	25	25
Onseng et al³⁵	2017	Patients with head and neck cancer receiving concurrent chemoradiation	47.3/49.6	RCTs	35days: 5 days a week throughout the 7 weeks of chemoradiation	At night after 21:00	10 mL of a 0.2% MLT niosome oral gargle plus 20 mg oral dosage	placebo	QOL (FACT—H&N), Mucositis rate, Mucositis severity (WHO-G)	19	20
Elsabagh et al²⁵	2019	Patients with head and neck cancer undergoing radiotherapy	57.8/55.9	RCTs	Six weeks	30 min before sleeping	20 mg oral MLT	Placebo	Stomatitis severity (WHO-G), Stomatitis rate, Pain (NRS)	20	20
Palmer et al³⁶	2019	Patients with breast cancer receiving chemotherapy	54.24/54.11	RCTs	10 days during treatment.	One hour before bedtime	20 mg oral MLT	Placebo	Pain (NRS), Sleep (PSQI), Depression (BDI)	18	18
Yennurajalingam et al⁴²	2019	Patients with advanced cancer with poor sleep quality	Not clearly	RCTs	14 days	At bedtime	20 mg oral MLT plus bright white light therapy	Bright white light therapy alone	Sleep (PSQI), insomnia (ISI), fatigue (FACIT-F), depression (HADS), QOL(FACT)	6	8
Palmer et al³⁷	2020	Patients with breast cancer undergoing chemotherapy after lumpectomy or mastectomy	54.24/54.11	RCTs	10 days: 3 days prior to chemotherapy and seven following days	One hour before bedtime	20 mg oral MLT	Placebo	Depressive symptoms (BDI-II), Sleep quality (PSQI), QOL (EORTC QLQ-C30)	18	18
Sedighi Pashaki et al³⁸	2021	Patients with breast cancer during adjuvant chemotherapy and radiotherapy	50.47/46.05	RCTs	8 weeks: from 1 week before until 1 month after the adjuvant radiotherapy	One hour before bedtime	18 mg oral MLT	Placebo	Fatigue (BFI)	38	36
Seely et al³⁹	2021	Patients with cancer following lung cancer resection	67.2/67.2	RCTs	One year after surgery	One hour before bedtime	20 mg oral MLT	Placebo	Fatigue (MFI-20), QOL(QLQ-LC13), Sleep (MOS), Depression (BDI 2), Pain (BPI)	356	353
Shahrokhi et al⁴⁰	2021	Patients with colorectal cancer undergoing chemotherapy with sleep disorder	63.63/64.11	RCTs	4 weeks of treatment	At bedtime	6 mg oral MLT	10 mg zolpidem	Sleep (GSQS, PSQI), Depression (HRSD)	45	45
Grutsch et al²⁶	2021	NSCLC patients under chemotherapy	60.3/63	RCTs	From intervention to death	At 8:00 hours or at 20:00 hours	20 mg oral MLT	Placebo	QOL(QLQ-C30), Fatigue (QLQ-C30), Pain (QLQ-C30), Sleep (PSQI)	20	18
A. Lozano et al ³²	2021	Patients with head and neck cancer undergoing radiation therapy and chemical treatment	59/56	RCTs	5 days a week, lasting 7 weeks	Not clearly	3% oral MLT gel plus standard symptomatic treatment for stomatitis	Placebo plus standard symptomatic treatment for stomatitis	Stomatitis severity (WHO-G), Stomatitis rate	40	39

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.