Table 2.

Clinical studies in which melatonin has been administered to cancer patients

First Author	Journal and year	Number of patients	Diagnosis	Test used for the diagnosis	Dose of melatonin administered to patients	Results
Hansen et al. [82]	BMJ Open 2012	260 (130 × 2)	Breast cancer, depression, anxiety, sleep disturbances and cognitive dysfunction.	Depressive Inventory Mayor, VAS (anxiety), sleep diary, Karolinska Sleepiness Scale, neuropsychological test battery.	6 mg/die	On going
Wang et al. [116]	Cancer Chemother Pharmacol 2012 (review)	761 pts	Solid tumor cancers		20 mg/die	Melatonin as an adjuvant therapy for cancer led to substantial improvements in tumor remission, 1-year survival, and alleviation of radiochemotherapy-related side effects.
Mills et al. [92]	J Pineal Res 2005 (review)	643 pts (between 1992 and 2003)	Solid tumor cancers		Not specified	Melatonin reduced the risk of death at 1 year (relative risk: 0.66, 95 % confidence interval: 0.59–0.73, I2 = 0 %, heterogeneity P ≤ 0.56). Effects were consistent across melatonin dose, and type of cancer.
Cerea G et al. [124]	Anticancer Res 2003	30 pts (15 + 15)	Metastatic colorectal cancer		20 mg/die	This preliminary study shows that the efficacy of weekly low-dose CPT-11 in pretreated metastatic colorectal cancer patients may be enhanced by a concomitant daily administration of the pineal hormone MLT
Lissoni P et al. [128]	Eur Urol 1997	14 pts	Metastatic prostate cancer		20 mg/die	A decrease in PSA serum levels greater than 50 % was obtained in 8/14 (57 %) patients, a survival longer than 1 year was achieved in 9/14 (64 %) patients. The concomitant administration of the pineal hormone MLT may overcome clinical resistance to LHRH analogs and improve clinical conditions in metastatic prostatic cancer patients.
Lissoni P et al. [121]	Oncology 1996	30 pts (15 + 15)	Brain glioblastoma		20 mg/die	Both the survival curve and the survival % at 1 year were significantly higher in patients treated with RT plus MLT than in those receiving RT alone (6/14 vs. 1/16).
Barni S et al. [129]	Oncology 1995	50	Metastatic colorectal cancer		40 mg/die	This study suggests low-dose subcutaneous IL-2 plus melatonin may be effective as a second-line therapy to induce tumor regression and to prolong % survival at 1 year in metastatic colorectal cancer patients progressing under 5-FU and folates.
Lissoni P et al. [130]	Br J Cancer 1995	14 pts	Metastatic breast cancer		20 mg/die	A partial response was achieved in 4/14 (28.5 %) patients (median duration 8 months. The concomitant administration of the pineal hormone MLT may induce objective tumor regressions in metastatic breast cancer patients refractory to TMX alone.
Lissoni P et al. [131]	Oncol Rep 1995	40 pts (20 + 20)	Breast cancer		20 mg/die	Partial response rate was significantly higher in patients treated with TMX and MLT than in those, who received TMX alone (7/19 vs 2/21, P < 0.05). Moreover, the survival % at 1 year was significantly higher in patients treated with TMX plus MLT than in those treated with TMX alone (12/19 vs 5/21, P < 0.01).
Lissoni P et al. [132]	Cancer 1994	50 (25 × 2)	Brain metastases		20 mg/die	The pineal hormone melatonin may be able to improve the survival time and the quality of life in patients with brain metastases due to solid tumors.
Aldeghi R et al. [133]	Eur J Cancer 1994	14 pts	Hepatocellular carcinoma		50 mg/die	Objective tumor regressions were obtained in 5/14 (36 %) patients.