***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Several experimental studies have shown that melatonin has an oncostatic action , either by stimulating host antitumor immune defenses or by directly inhibiting the growth of some cancer histotypes , including melanoma . Our previous clinical studies demonstrated that melatonin may induce stabilization of the disease in untreatable metastatic solid tumor patients , and these results have been confirmed by others , at least in patients with metastatic melanoma . On the contrary , at present there are no data related to the possible efficacy of melatonin as an adjuvant endocrine therapy . This study was performed to investigate the impact of melatonin therapy on the disease-free survival ( DFS ) in melanoma patients surgically treated for regional node recurrence . The study included 30 node-relapsed melanoma patients , who were r and omized to receive no treatment or adjuvant therapy of melatonin  ( 20 mg/day orally in the evening ) every day until disease progression . After a median follow up of 31 months , the percent of DFS was significantly higher in melatonin-treated individuals than in controls . The DFS curve was also significantly longer in melatonin group than in controls . No melatonin-related toxicity was observed . This preliminary study suggests that an adjuvant endocrine therapy with melatonin may be effective in preventing disease progression in node-relapsed melanoma patients Our previous experimental studies have shown that the best approach to increase the biological anti-tumour activity of interleukin 2 ( IL-2 ) is not co-administration of another cytokine , but the association with immunomodulating neurohormones , in an attempt to reproduce the physiological links between psychoendocrine and immune systems , which play a fundamental role in the regulation of the immune responses . In particular , the association with the pineal neurohormone melatonin ( MLT ) has been shown to cause tumour regressions in neoplasms that are generally non-responsive to IL-2 alone . To confirm these preliminary results , a clinical trial was performed in locally advanced or metastatic patients with solid tumours other than renal cell cancer and melanoma . The study included 80 consecutive patients , who were r and omised to be treated with IL-2 alone subcutaneously  ( 3 million IU day-1 at 8.00 p.m. 6 days a week for 4 weeks ) or IL-2 plus MLT  ( 40 mg day-1 orally at 8.00 p.m. every day starting 7 days before IL-2 ) . A complete response was obtained in 3/41 patients treated with IL-2 plus MLT and in none of the patients receiving IL-2 alone . A partial response was achieved in 8/41 patients treated with IL-2 plus MLT and in only 1/39 patients treated with IL-2 alone . Tumour objective regression rate was significantly higher in patients treated with IL-2 and MLT than in those receiving IL-2 alone ( 11/41 vs 1/39 , P < 0.001 ) . The survival at 1 year was significantly higher in patients treated with IL-2 and MLT than in the IL-2 group ( 19/41 vs 6/39 , P < 0.05 ) . Finally , the mean increase in lymphocyte and eosinophil number was significantly higher in the IL-2 plus MLT group than in patients treated with IL-2 alone ; on the contrary , the mean increase in the specific marker of macrophage activation neopterin was significantly higher in patients treated with IL-2 alone . The treatment was well tolerated in both groups of patients . This study shows that the concomitant administration of the pineal hormone MLT may increase the efficacy of low-dose IL-2 subcutaneous therapy BACKGROUND The MIRCIT trial was a r and omized , double-blind , placebo-controlled study of advanced Non-small cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients were r and omized to receive 10 mg or 20 mg of melatonin or placebo .  Assessment of health-related quality of life ( HRQoL ) was completed at baseline , and at 2 , 3 and 7 months . Survival and adverse events were collected . DNA damage marker 8-oxo-7,8-dihydro-2'-deoxyguanosine ( 8-oxodG ) was measured during the first three months of chemotherapy . RESULTS Patients in the melatonin-treated  group had better adjusted HRQoL scores , with a slightly significantly better score ( 2.69 points , 95 % confidence interval (CI)=0.01 - 5.38 , p=0.049 ) being found in social well-being . Median survival was 7.3 months ( 95 % CI=3.42 - 11.14 ) without significant difference . A great amont of DNA damage marker was observed in the placebo-treated group , and this was associated with lower survival ( r(2)=-0.656 , p=0.02 ) , implying the protective effect of melatonin in healthy cells . CONCLUSION Melatonin in combination with chemotherapy did not affect survival and adverse events of advanced patients with NSCLC , but there was a trend for better Recent studies suggest that the pineal hormone melatonin may reduce chemotherapy-induced immune and bone marrow damage . In addition , melatonin may exert potential oncostatic effects either by stimulating host anticancer immune defenses or by inhibiting tumor growth factor production . On this basis , we have performed a r and omized study of chemotherapy alone vs. chemotherapy plus melatonin in advanced non-small cell lung cancer patients ( NSCLC ) with poor clinical status . The study included 70 consecutive advanced NSCLC patients who were r and omized to receive chemotherapy alone with cisplatin ( 20 mg/m2/day i.v . for 3 days ) and etoposide ( 100 mg/m2/day i.v . for 3 days ) or chemotherapy plus melatonin ( 20 mg/day orally in the evening ) . Cycles were repeated at 21-day intervals . Clinical response and toxicity were evaluated according to World Health Organization criteria . A complete response ( CR ) was achieved in 1/34 patients concomitantly treated with melatonin and in none of the patients receiving chemotherapy alone . Partial response ( PR ) occurred in 10/34 and in 6/36 patients treated with or without melatonin , respectively . Thus , the tumor response rate was higher in patients receiving melatonin ( 11/34 vs. 6/35 ) , without , however , statistically significant differences . The percent of 1-year survival was significantly higher in patients treated with melatonin plus chemotherapy than in those who received chemotherapy alone ( 15/34 vs. 7/36 , P < 0.05 ) . Finally , chemotherapy was well tolerated in patients receiving melatonin , and in particular the frequency of myelosuppression , neuropathy , and cachexia was significantly lower in the melatonin group . This study shows that the concomitant administration of melatonin may improve the efficacy of chemotherapy , mainly in terms of survival time , and reduce chemotherapeutic toxicity in advanced NSCLC , at least in patients in poor clinical condition Background Fatigue and sleep problems are prevalent in cancer patients and can be associated with disruption of circadian rhythmicity . In this prospect i ve phase II trial , we sought to assess the effect of melatonin on circadian biomarkers , sleep , and quality of life in breast cancer patients . Methods Thirty-two patients with metastatic breast cancer , receiving hormonal or trastuzumab therapy , took 5 mg of melatonin at bedtime for 2 months . Before starting and after 2 months on melatonin therapy , sleep and circadian rhythmicity were assessed by actigraphy , diurnal patterns of serum cortisol , and the expression of the core clock genes PER2 and BMAL1 in peripheral blood mononuclear cells . The European Organisation for Research and Treatment of Cancer ( EORTC ) QLQ-C30 question naire was completed for subjective parameters . Results Bedtime melatonin was associated with a significant improvement in a marker of objective sleep quality , sleep fragmentation and quantity , subjective sleep , fatigue severity , global quality of life , and social and cognitive functioning scales . Morning clock gene expression was increased following bedtime melatonin intake . Melatonin did not affect actigraphy measure of circadian rhythmicity , or the diurnal cortisol pattern . Conclusion These results invite further investigation of melatonin as a potentially useful therapeutic agent for improving sleep and quality of life in cancer patients Experimental data have suggested that the pineal hormone melatonin ( MLT ) may counteract chemotherapy-induced myelosuppression and immunosuppression . In addition , MLT has been shown to inhibit the production of free radicals , which play a part in mediating the toxicity of chemotherapy . A study was therefore performed in an attempt to evaluate the influence of MLT on  chemotherapy toxicity . The study involved 80 patients with metastatic solid tumors who were in poor clinical condition ( lung cancer : 35 ; breast cancer : 31 ; gastrointestinal tract tumors : 14 ) . Lung cancer patients were treated with cisplatin and etoposide , breast cancer patients with mitoxantrone , and gastrointestinal tract tumor patients with 5-fluorouracil plus folates . Patients were r and omised to receive chemotherapy alone or chemotherapy plus MLT ( 20 mg/day p.o . in the evening ) . Thrombocytopenia was significantly less frequent in patients concomitantly treated with MLT .  Malaise and asthenia were also significantly less frequent in patients receiving MLT . Finally , stomatitis and neuropathy were less frequent in the MLT group , albeit without statistically significant differences . Alopecia and vomiting were not influenced by MLT . This pilot study seems to suggest that the concomitant administration of the pineal hormone MLT during chemotherapy may prevent some chemotherapy-induced side-effects , particularly myelosuppression and neuropathy . Evaluation of the impact of MLT on  chemotherapy efficacy will be the aim of future clinical investigations It is known since many years that the pineal hormone melatonin ( MLT ) may play anticancer activity through several mechanisms , including antiproliferative and immunostimulating effects . Moreover , it exerts an important antioxidant action . Therefore , MLT could be useful in the treatment of human neoplasms , either alone or in association with chemotherapy . The present study was performed to evaluate the influence of a concomitant MLT administration on efficacy and toxicity of several chemotherapeutic combinations in metastatic solid tumor patients , suffering from non-small cell lung cancer ( NSCLC ) or gastrointestinal tumors . The study included 370 patients who were r and omized to receive chemotherapy alone or chemotherapy plus MLT ( 20 mg/day orally in the evening every day ) . NSCLC patients received cisplatin ( CDDP ) plus etoposide or CDDP plus gemcitabine .  Colorectal cancer patients were treated with oxaliplatin plus 5-fluorouracil ( 5-FU ) , or weekly CPT-11 or 5-FU and folates ( FA ) . Finally , gastric cancer patients received CDDP , epirubicin , 5-FU and FA or weekly 5-FU plus FA . The overall tumor regression rate achieved in patients concomitantly treated with MLT was significantly higher than that found in those treated with chemotherapy alone . Moreover , the 2-year survival rate was significantly higher in patients concomitantly treated with MLT . These results confirm in human the anticancer therapeutic properties of the pineal hormone MLT , which may enhance the efficacy of the st and ard anticancer chemotherapies At present , there is no effective medical therapy in metastatic nonsmall cell ( NSC ) lung cancer patients who progressed under a first-line chemotherapy containing cisplatin .  Since recent data have demonstrated the antineoplastic properties and the lack of toxicity of the pineal hormone melatonin ( MLT ) , a r and omized study was design ed to evaluate the influence of an MLT treatment ( 10 mg/day orally at 7.00 p.m. ) on the survival time at 1 year from the progression under chemotherapy in respect to supportive care alone in a group of metastatic NSC lung cancer patients , who did not respond to a first-line chemotherapy containing cisplatin .  The study includes 63 consecutive metastatic NSC lung cancer patients , who were r and omized to receive MLT ( n = 31 ) or supportive care alone ( n = 32 ) . The percentage of both stabilizations of disease and survival at 1 year was significantly higher in patients treated with MLT than in those treated only with supportive care . No drug-related toxicity was seen in patients treated with MLT , who , on the contrary , showed a significant improvement in performance status . This r and omized study shows that the pineal hormone MLT may be successfully administered to prolong the survival time in metastatic NSC lung cancer patients who progressed under a first-line chemotherapy with cisplatin  , for whom no other effective therapy is available up to now Several experiments have demonstrated that pineal gl and plays a physiological anticancer role . Melatonin ( MLT ) , its most investigated hormone , is a natural anticancer agent . However , MLT would not be the only endocrine molecule responsible for the anticancer property of the pineal gl and . In fact , another pineal indole hormone , the 5-methoxytryptamine ( 5-MTT ) , has appeared to exert in vitro an antitumour activity superior to that of MLT itself . Previous studies have already shown the therapeutic anticancer action of MLT in association with chemotherapy also in human neoplasms . This study was performed to evaluate the influence of 5-MTT at physiological doses ( 1 mg/day orally during light phase ) on the efficacy of chemotherapy with cispl 
    Output:
    
Conclusion MLT exerts positive influence in tumor therapeutic strategies , including improving tumor remission rate and overall survival rate , while reducing the incidence of chemotherapy side effects .