Effect of Mirtazapine Versus Placebo in Patients With Non-small Cell Lung Cancer and Anorexia

Lung cancer is the leading cause of cancer death in Mexico and the world. One of the comorbidities most commonly associated with this type of malignancy is malnutrition, which occurs in approximately 40-50% of newly diagnosed cases. In addition to its high incidence, malnutrition in patients with cancer is of great relevance due to the negative effect that this entails on the quality of life and the prognosis of patients, as well as the increase in toxicity associated with oncological treatment. Malnutrition is a pathological state in which the deficiency in the adequate contribution of energy contributes to its development, producing a systemic catabolic state; Its etiology is variable, however, in most patients malnutrition is associated with a lack of appetite, which is called anorexia. Mirtazapine is a tetracyclic antidepressant which has been widely used for the treatment of depression. Several clinical studies have proven its efficacy in this indication, with more than 5000 patients endorsing its clinical effect compared to placebo, other tetracyclic antidepressants and trazodone. In addition to its effect on mood, it has been observed that mirtazapine, used in standard doses, induces weight gain, increasing appetite and food consumption compared to patients receiving placebo. The increase in appetite with consequent weight gain and increased food intake may be due to the blocking of 5HT1b, 5-HT2, 5-HT3, H1 receptors, involved in the regulation of appetite. A pilot study of 2 doses of mirtazapine (15 or 30 mg per day) in ambulatory cancer patients with pain and other discomforts suggests that it provides a significant improvement in quality of life, particularly in weight and energy intake. Recently, another phase II study observed that 57% of oncology patients, ambulatory, non-depressed, increased their appetite and body weight when treated with mirtazapine for 4 weeks. Despite these encouraging data, the study included a small sample of patients, so it is not possible to generate robust conclusions from these data. The objective of this protocol is to conduct a prospective, randomized, double-blind clinical trial to evaluate the effect of Mirtazapine on appetite, nutritional status and quality of life in patients with anorexia associated with lung cancer. The sample would include 86 patients, 43 patients with Mirtazapine and 43 sith placebo for 8 weeks, with an inducing dose of 15 mg to a máximum of 30 mg. The methodology for conducting this study consists of recruiting patients diagnosed with anorexia according to the anorexia-cachexia (ACS) scale, which has a cut-off point specifically validated for lung cáncer. Once the patient is selected, they are invited to participate in the study and an informed consent is requested. Subsequently a subjective global evaluation is performed, a 24-hour reminder of energy consumption, evaluation of anthropometric measures (weight, height,% weight loss, body mass index), evaluation of body composition (% fat, fat-free mass and phase angle), common gastrointestinal adverse effects of chemotherapy according to CTCAE, an evaluation of anxiety and depression (HADS) , as well as determination of quality of life through the questionnaire "The European organization for research and treatment of cancer quality of life questionnaire (QLQ) -C30 and (QLQ) LC-13", validated for Mexican population. All determinations will be made at baseline, at 4 and at 8 weeks. All the variables are going to be evaluated inside each groups and between groups. It´s going to be considered significant p ≤ 0.05.