Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status

Lissoni, Paolo; Barni, Sandro; Mandalà, Mario; Ardizzoia, Antonio; Paolorossi, F.; Vaghi, Massimo; Longarini, Raffaella; Malugani, Fabio; Tancini, G

doi:10.1016/s0959-8049(99)00159-8

Cited by 227 publications

(191 citation statements)

References 20 publications

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“…(19,20,21,22,23,11,24,25,26,27,28,29,30,31,32,33) Three independent randomized trials, including this trial, have been run. (34,35) It is noteworthy that all of the trials from Lissoni and colleagues have had positive outcomes and, as of yet, there have been no confirmatory publications from outside of his group.…”

Section: Discussionmentioning

confidence: 99%

Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

Berk¹,

Berkey²,

Rich³

et al. 2007

International Journal of Radiation Oncology*Biology*Physics

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Backround-RTOG 0119 was a Phase II randomized trial for RTOG RPA Class 2 patients with brain metastases to determine if high-dose melatonin improves survival over historical controls, and to determine if the time of day melatonin was given affects its toxicity or efficacy.Methods-RTOG RPA class 2 patients with brain metastases were randomized to 20 mg of melatonin given either in the morning (8-9 am) or evening (8-9 pm). All patients received radiation therapy (30 Gy in 10 fractions) in the afternoon. Melatonin was continued until neurological deterioration or death. The primary endpoint was overall survival time. Neurological deterioration as reflected by the Mini-Mental Status Exam was also measured.Results-Neither of the randomized groups had survival distributions that differed significantly from the historic control of patients treated with whole brain radiotherapy The median survivals of Corresponding Author: Lawrence Berk, MD, PhD, Radiation Oncology, Moffitt Cancer Center at Tampa General Hospital, 2 Columbia Dr., Tampa, FL 39606, E-mail: Berklb@moffitt.usf.edu. No conflicts of interest All patients gave IRB approved informed consent prior to enrolling on this trial.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access IntroductionMelatonin, an indoleamine molecule (N-acetyl, 5-methoxytryptamine) plays an important role in a number of processes including circadian rhythm regulation, sleep disorders, seasonal reproduction, retinal physiology, immune function, intermediary metabolism (1,2) and carcinogenesis. (3) It is also a highly efficient and potent free radical scavenger/antioxidant molecule and physiological blood levels of correlate with the total antioxidant capacity of the serum. (4) Oral ingestion of microgram amounts of melatonin results in near physiological nocturnal blood levels of melatonin. (5,6) The oral bioavailability of milligram doses of oral melatonin from nutritional supplements is about 15% (7) and results in supra-physiological melatonin levels.Numerous studies have demonstrated that physiological and pharmacological blood concentrations of melatonin inhibit tumorigenesis in a variety of in vivo and in vitro experimental models of neoplasia. (6,8,9) A preliminary study demonstrated that pretreatment of rats bearing hepatomas, for two weeks prior to a single dose of radiation administered just prior to lights off, with a non-tumor inhibiting dose of melatonin also given just before lights off, had a marked radiosensitizing effect. Pretreatment of tumor-bearing rats with AM doses of melatonin were ineffective. (10) The gre...

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Section: Discussionmentioning

confidence: 99%

Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

Berk¹,

Berkey²,

Rich³

et al. 2007

International Journal of Radiation Oncology*Biology*Physics

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“…Lissoni's group reports that melatonin reduces the toxicity of various chemotherapeutic agents, including Cisplatin, Etoposide, Anthracyclines, and 5-Flourouracil. They found a statistically significant reduction in treatment-related adverse events, such as myelosuppression, neurotoxicity, nephrotoxicity, cardiotoxicity, and asthenia (Lissoni et al, 1992(Lissoni et al, , 1994(Lissoni et al, , 1997(Lissoni et al, , 1999.…”

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confidence: 99%

Circadian function in patients with advanced non-small-cell lung cancer

et al. 2005

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This study aimed to evaluate whether patients with advanced non-small-cell lung cancer experience disrupted rest -activity daily rhythms, poor sleep quality, weakness, and maintain attributes that are linked to circadian function such as fatigue. This report describes the rest -activity patterns of 33 non-small-cell lung cancer patients who participated in a randomised clinical trial evaluating the benefits of melatonin. Data are reported on circadian function, health-related quality of life (QoL), subjective sleep quality, and anxiety/depression levels prior to randomisation and treatment. Actigraphy data, an objective measure of circadian function, demonstrated that patients' rest -activity circadian function differs significantly from control subjects. Our patients reported poor sleep quality and high levels of fatigue. Ferrans and Powers QoL Index instrument found a high level of dissatisfaction with healthrelated QoL. Data from the European Organization for Research and Treatment for Cancer reported poor capacity to fulfil the activities of daily living. Patients studied in the hospital during or near chemotherapy had significantly more abnormal circadian function than those studied in the ambulatory setting. Our data indicate that measurement of circadian sleep/activity dynamics should be accomplished in the outpatient/home setting for a minimum of 4 -7 circadian cycles to assure that they are most representative of the patients' true condition. We conclude that the daily sleep/activity patterns of patients with advanced lung cancer are disturbed. These are accompanied by marked disruption of QoL and function. These data argue for investigating how much of this poor functioning and QoL are actually caused by this circadian disruption, and, whether behavioural, light-based, and or pharmacologic strategies to correct the circadian/sleep activity patterns can improve function and QoL.

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“…2 Moreover, it can also act synergistically with anticancer drugs, enhancing their effectiveness while reducing their side effects. 12 Despite the fact that evidence for circadian and seasonal effects on cancer progression exist, thus far there are no definitive pathogenetic mechanisms for this observation. Consequently, theories that lead in this direction remain highly speculative.…”

Section: Discussionmentioning

confidence: 99%

Seasonal variability in the incidence of carcinomatous meningitis

Koutras¹,

Sakellakis²,

Makatsoris³

et al. 2015

JNS

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OBJECT The aim of the study was to investigate whether there are seasonal differences in the occurrence of carcinomatous meningitis (CM), with a greater prevalence of the disease in months with higher temperatures. METHODS The authors searched the records of all patients with a diagnosis of CM from 1998 until 2013 at the University Hospital of Patras, Greece. The date of hospitalization was extracted for each patient. The cases were divided into 2 categories depending on the time of CM diagnosis. Based on the official data regarding the annual temperature distribution in this region, the authors divided the patients into 2 groups. The first group consisted of cases diagnosed with CM from October 15 to April 15 (cold climate and shorter daytime duration), whereas the second group comprised patients diagnosed between April 15 and October 15 (warm climate and longer daytime duration). RESULTS Overall, 44 confirmed cases of CM were found. The most common type of malignancy associated with the development of CM was breast cancer (27 patients), while the second most common tumor was lung carcinoma (11 patients). The median interval between the time of initial cancer diagnosis and CM was 4.5 years. Thirty-one patients were diagnosed with CM during the period between April 15 and October 15, while the remaining 13 patients developed CM between October 15 and April 15, a significant difference (p = 0.01). CONCLUSIONS Significantly more patients developed CM during the warm season of the year. To the authors' knowledge, this is the first study to provide evidence for the potential seasonal variability in CM incidence. However, these results should be validated prospectively in larger cohorts.

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Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status

Cited by 227 publications

References 20 publications

Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

Circadian function in patients with advanced non-small-cell lung cancer

Seasonal variability in the incidence of carcinomatous meningitis

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