Effects of Melatonin on Appetite and Other Symptoms in Patients With Advanced Cancer and Cachexia: A Double-Blind Placebo-Controlled Trial

The University of Texas MD Anderson Cancer Center, Houston, TX.
Journal of Clinical Oncology (Impact Factor: 18.43). 02/2013; 31(10). DOI: 10.1200/JCO.2012.43.6766
Source: PubMed


PURPOSEPrior studies have suggested that melatonin, a frequently used integrative medicine, can attenuate weight loss, anorexia, and fatigue in patients with cancer. These studies were limited by a lack of blinding and absence of placebo controls. The primary purpose of this study was to compare melatonin with placebo for appetite improvement in patients with cancer cachexia. PATIENTS AND METHODS
We performed a randomized, double-blind, 28-day trial of melatonin 20 mg versus placebo in patients with advanced lung or GI cancer, appetite scores ≥ 4 on a 0 to 10 scale (10 = worst appetite), and history of weight loss ≥ 5%. Assessments included weight, symptoms by the Edmonton Symptom Assessment Scale, and quality of life by the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire. Differences between groups from baseline to day 28 were analyzed using one-sided, two-sample t tests or Wilcoxon two-sample tests. Interim analysis halfway through the trial had a Lan-DeMets monitoring boundary with an O'Brien-Fleming stopping rule. Decision boundaries were to accept the null hypothesis of futility if the test statistic z < 0.39 (P ≥ .348) and reject the null hypothesis if z > 2.54 (P ≤ .0056).ResultsAfter interim analysis of 48 patients, the study was closed for futility. There were no significant differences between groups for appetite (P = .78) or other symptoms, weight (P = .17), FAACT score (P = .95), toxicity, or survival from baseline to day 28. CONCLUSION
In cachectic patients with advanced cancer, oral melatonin 20 mg at night did not improve appetite, weight, or quality of life compared with placebo.

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    • "Del Fabbro et al38 performed a randomized, double-blind, 28-day trial of melatonin 20 mg versus placebo in patients with advanced lung or gastrointestinal cancer and a history of weight loss ≥5%. Assessments included weight, symptoms on the Edmonton Symptom Assessment Scale, and quality of life using the Functional Assessment of Anorexia/Cachexia Therapy questionnaire. "
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    ABSTRACT: Cancer-related anorexia and cachexia syndrome (CACS) is a complex multifactorial condition, with loss of lean body mass, chronic inflammation, severe metabolic derangements, reduced food intake, reduced physical activity, and poor quality of life as key symptoms. Cachexia recognizes different phases or stages, moving from precachexia through overt cachexia to advanced or refractory cachexia. The purpose of this review is to describe currently effective approaches for the treatment of cachexia, moving forward to drugs and treatments already shown to be effective but needing further clinical trials to confirm their efficacy. We then introduce novel promising investigational drugs and approaches which, based on a strong rationale from the most recent data on the molecular targets/pathways driving the pathophysiology of cachexia, need to be tested either in currently ongoing or appropriate future clinical trials to confirm their clinical potential. Although different drugs and treatments have been tested, we can speculate that a single therapy may not be completely successful. Indeed, considering the complex clinical picture and the multifactorial pathogenesis of CACS, we believe that its clinical management requires a multidisciplinary and multitargeted approach. In our opinion, appropriate treatment for cachexia should target the following conditions: inflammatory status, oxidative stress, nutritional disorders, muscle catabolism, immunosuppression, quality of life, and above all, fatigue. A comprehensive list of the most interesting and effective multitargeted treatments is reported and discussed, with the aim of suggesting the most promising with regard to clinical outcome. A critical issue is that of testing therapies at the earliest stages of cachexia, possibly at the precachexia stage, with the aim of preventing or delaying the development of overt cachexia and thereby obtaining the best possible clinical outcome for patients.
    Drug Design, Development and Therapy 08/2013; 7:645-56. DOI:10.2147/DDDT.S39771 · 3.03 Impact Factor
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    Journal of Clinical Oncology 02/2013; 31(10). DOI:10.1200/JCO.2012.48.3149 · 18.43 Impact Factor
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    ABSTRACT: Dysregulated inflammatory responses are important in a multitude of chronic ailments including cancer. Disease progression in cancer is dependent on the complex interaction between the tumor and the host microenvironment including inflammatory responses, as both the tumor and microenvironment components can produce cytokines that act on multiple target sites where they promote a complex cascade of biological responses. Patients with cancer-associated cachexia (CAC) suffer from a dramatic loss of skeletal muscle and adipose tissue and are, therefore, precluded from many forms of therapeutic interventions, including radiotherapy. The cytokines that have been linked to the promotion of the cachectic response also play a role in radiation resistance. The major changes at the cytokine level are in part due to transcriptional regulatory alterations possibly due to epigenetic modifications. Here we summarize the role of inflammatory pathways in CAC and discuss the potential link between cachexia induction and radiation resistance.
    Molecular Cancer Research 06/2013; 11(9). DOI:10.1158/1541-7786.MCR-13-0189 · 4.38 Impact Factor
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