Distribution, function and physiological role of melatonin in the lower gut

Table 4 Clinical trials using melatonin in patients with colorectal cancer

Authors	n	Disease	Study design	Dose	Results and conclusion
Lissoni et al[140]	18	Rectal cancer	Randomized to melatonin, melatonin + 5-methoxytryptamine or melatonin + IL-2, 5 wk	20 mg/od	Melatonin had no effect on radiation-induced lymphocytopenia
Lissoni[133]	152	CRC	Randomized to oxaliplatin/5-Fu or CPT-11/FS/5-Fu with or without melatonin	20 mg/od	Melatonin significantly reduced the occurrence of cachexia, thrombocytopenia, neurotoxicity and asthenia
Persson et al[139]	8	CRC	Randomized to fish oil or melatonin (4 wk) followed by 4 wk fish oil with melatonin	18 mg/od	Melatonin had no effect on serological inflammation markers
Cerea et al[135]	30	CRC	Randomized to CPT-11 or CPT-11 plus melatonin 9 wk	20 mg/od	Disease-control higher in CPT-11 + melatonin group
Lissoni et al[120]	7	CRC	Daily melatonin for at least 2 mo	20 mg/od	Melatonin may control tumor growth by reducing VEGF secretion
Lissoni et al[134]	25	CRC	Randomized to 5-Fu/FS or 5-Fu/FS + melatonin. 5 cycles of 28 d	20 mg/od	Melatonin reduces toxicity and increases efficacy of 5-Fu/FS chemotherapy
Lissoni et al[138]	8	CRC	Randomized to melatonin or melatonin + Aloe vera tincture until progression	20 mg/od	Melatonin + Aloe vera stabilized disease and increased survival in end-stage patients
Barni et al[137]	50	CRC	Randomized to BSC or BSC combined with low-dose IL-2 + melatonin 4 wk	40 mg/od	Low-dose IL-2 + melatonin induced tumor regression and prolonged survival in second-line treatment
Lissoni et al[136]	19	CRC	Randomized to IL-2 or IL-2 + melatonin 4 wk	40 mg/od	Melatonin enhanced the activity of IL-2, induced tumour regression, prolonged progression-free survival and overall survival

CRC: Colorectal cancer; od: Once daily; BSC: Best supportive care; VEGF: Vascular endothelial growth factor.