Mirtazapine as Appetite Stimulant in Patients With Non-Small Cell Lung Cancer and Anorexia: A Randomized Clinical Trial.

Importance: Currently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context. Objectives: To assess the effect of mirtazapine on appetite and energy consumption in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: This randomized, double-blind, placebo-controlled clinical trial including adults was performed in a tertiary cancer care center from August 2018 to May 2022 with a follow-up of 8 weeks. Overall, 134 patients were screened; 114 were assessed for eligibility and 28 were excluded. Interventions: Patients were randomized in a 1:1 ratio to receive mirtazapine, 15 mg, or placebo for 2 weeks followed by a dose escalation to 30 mg until week 8 or placebo. Both groups received nutritional assessment and dietary advice. Main outcomes and measures: Appetite was assessed by the Anorexia Cachexia Scale and energy intake. Dietary parameters were evaluated at baseline, 4 weeks, and 8 weeks, with a 24-hour dietary recall, and energy quantification based on the Mexican system of nutritional equivalents. Results: A total of 86 patients met the inclusion criteria and were randomized to the placebo (n = 43) or the mirtazapine group (n = 43). The mean (SD) age was 63.5 (11.2) years, 41 were women (57.7%) and had adenocarcinoma, Eastern Cooperative Oncology Group performance status scale score of 1, stage IV NSCLC, and were receiving first-line treatment. Baseline characteristics were similar between groups. There was no difference in appetite scores in patients who received mirtazapine or placebo after 4 and 8 weeks. After 4 weeks, mirtazapine significantly increased energy intake (379.3 kcal; 95% CI, 1382.6-576.1; P < .001) including proteins (22.5 g; 95% CI, 11.5-33.4; P = .001), carbohydrates (43.4 g; 95% CI, 13.1-73.8; P = .006), and fats (13.2 g; 95% CI, 6.0-20.4; P = .006). Fats intake was significantly higher in patients in the mirtazapine group (14.5 g vs 0.7 g; P = .02) after 8 weeks. The mirtazapine group significantly decreased the proportion of patients with sarcopenia (82.8% vs 57.1%, P = .03) at 8 weeks. Patients on mirtazapine tolerated the treatment well, but reported a higher perception of nightmares at 2 weeks based on a 10 cm VAS score (0 [25th-75th percentile, 0-1] vs 0 [25th-75th percentile, 0-0] in the control group; P = .009) but this finding was nonsignificant after 4 and 8 weeks. Conclusion and Relevance: In this randomized clinical trial of patients with advanced NSCLC, there was no difference in appetite scores in all patients who received mirtazapine or placebo, but the mirtazapine group had a significant increase in energy intake through the 4- and 8-week follow-up, mainly in fat intake, which is a better and crucial source of energy. The addition of mirtazapine in the treatment of patients with advanced NSCLC and anorexia may help these patients achieve their energy requirements and improve health-related quality of life, specifically emotional and cognitive functioning. Trial Registration: ClinicalTrials.gov Identifier: NCT04748523.

Current advancements in pharmacotherapy for cancer cachexia.

INTRODUCTION: Cancer cachexia is a multifactorial metabolic syndrome associated with a pathophysiology intertwined with increased inflammatory response, anorexia, metabolic dysregulation, insulin resistance, and hormonal alterations, which together generate a negative energy balance in favor of catabolism. The development of therapeutic strategies to treat cancer cachexia has always been related to clinical interventions with increased food intake/supplementation, physical exercise regimens, and/or medication to attenuate catabolism and increase the anabolic response. However, the approval of drugs by regulatory agencies has always been a challenge. AREAS COVERED: This review outlines the main pharmacotherapy findings in cancer cachexia as well as the ongoing clinical trials that have evaluated changes in body composition and muscle function. The National Library of Medicine (PubMed) was used as search tool. EXPERT OPINION: The pharmacological therapy for cachexia should be focused on improving body composition, muscle function, and mortality, although none of the compounds used so far was able to demonstrate positive results beyond increased appetite and improvements in body composition. Ponsegromab (GDF15 inhibitor), a new compound that has just entered a phase II clinical trial, is a promising candidate to treat cancer cachexia and may produce exciting results if the study can be conducted as planned.

Appetite stimulants for patients with cancer: current evidence for clinical practice.

The incidence of neoplastic diseases has increased worldwide, with an estimated global burden of 19.3 million incident cases and 10 million deaths in 2020-a considerable increase compared with 9.6 million deaths in 2018. One of the most prevalent problems faced by patients with cancer and their physicians is malnutrition. It is estimated that patients with cancer have important nutritional alterations in 25% to 70% of cases, which directly affects many spheres of patient care and well-being, including quality of life, treatment toxicity, and survival outcomes. Despite the overwhelming need to address this pressing issue, current evidence in terms of pharmacologic interventions for cancer-related anorexia remains inconclusive, and there is no current standard of care for patients with cancer-related anorexia. Nonetheless, international guidelines recommend promoting anabolism through nutritional, physical, and pharmacologic therapies. In this review, the available information is summarized regarding pharmacologic therapies to treat cancer-related anorexia and findings are highlighted from a clinical stance.

An overview of anamorelin as a treatment option for cancer-associated anorexia and cachexia.

INTRODUCTION: Cancer cachexia is a complex multifaceted syndrome involving functional impairment, changes in body composition, and nutritional disorders. The treatment of cancer cachexia can be based on these three domains of the syndrome. Phase II and III trials of anamorelin, a ghrelin mimetic agent, have been shown to increase body weight in patients with cancer cachexia, mainly by increasing muscle and fat mass. Anamorelin has been shown to improve anorexia scores. AREAS COVERED: This review aims to outline the effect of anamorelin on body composition and functional parameters as well as to discuss the clinical importance of these alterations in patients with cancer cachexia. EXPERT OPINION: To date, there is no treatment approved to enhance body composition and functional parameters in patients with cancer cachexia. Anamorelin, the most advanced therapy to treat cachexia, has not yielded convincing results in all aspects of the syndrome. In particular, no effect has been noted on physical function and long-term survival. Along with these essential improvements for future interventions with anamorelin, subsequent studies must address other etiologies of cancer, rather than non-small cell lung cancer, and add complementary therapies, such as exercise training and nutritional interventions, in an attempt to overcome cancer cachexia.

Condutas para o manejo da anorexia em cuidados paliativos: revisão integrativa / Management approach for anorexia in palliative care: an integrative literature review / Conducta para el manejo de anorexia en cuidado paliativo: revisión integradora

Objetivo: Identificar as evidências científicas acerca das condutas para o manejo da anorexia em cuidados paliativos. Métodos: Trata-se de uma revisão integrativa, cujo levantamento bibliográfico dos dados deu-se através da pesquisa em quatro bases de dados/bibliotecas virtuais. Incluíram-se artigos em português, inglês e espanhol, publicados nos últimos dez anos e com o texto completo disponível. Resultados: Foram elegíveis 25 artigos, e foram atribuídos dois eixos temáticos para melhor ilustrar os dados encontrados: o manejo farmacológico e o não-farmacológico. Corticosteroides, progestinas, anamorelina e dronabinol foram os fármacos mais pesquisados para o controle da anorexia, com maiores evidências de eficácia nos 3 primeiros. No contexto não-farmacológico, o aconselhamento nutricional foi a medida mais indicada, incluindo a fortificação de alimentos e uso de suplementos e a nutrição artificial mais controversa. Conclusão: Os achados desta revisão podem colaborar para a elaboração de protocolos para o manejo da anorexia em cuidados paliativos

Objective: The study's main goal has been to identify scientific evidence on the management of anorexia in palliative care. Methods: This is an integrative review, whose data collection occurred by researching four databases/virtual libraries. Articles in Portuguese, English, and Spanish, published over the last ten years and with the full text available, were included. Results: 25 articles were selected, and two thematic axes were assigned to better illustrate the data found: pharmacological and non-pharmacological management. Corticosteroids, progestins, anamorelin, and dronabinol were the most-researched drugs for the control of anorexia, with greater evidence of effectiveness for the first three. In the non-pharmacological treatment, nutritional counseling was the most recommended measure, including the fortification of foods and the use of supplements and the more-controversial artificial nutrition. Conclusion: The findings of this review may aid in the development of protocols for the treatment of anorexia in palliative care

Objetivo: El propósito principal del estudio ha sido identificar evidencia científica sobre el manejo de la anorexia en los cuidados paliativos. Métodos: Esta es una revisión integradora, cuya investigación bibliográfica de datos ocurrió mediante búsqueda en cuatro bases de datos/bibliotecas virtuales. Se incluyeron artículos en portugués, inglés y español, publicados en los últimos diez años y con texto completo disponible. Resultados: Fueron elegibles 25 artículos, siendo atribuidos dos ejes temáticos para ilustrar mejor los datos encontrados: el manejo farmacológico y el no farmacológico. Corticosteroides, progestinas, anamorelina y dronabinol han sido los fármacos más buscados para el control de la anorexia, con mayores evidencias de eficacia en los 3 primeros. En el contexto no farmacológico, el asesoramiento nutricional fue la medida más indicada, incluyendo la fortificación de alimentos y uso de suplementos y la nutrición artificial más controversia. Conclusión: Los hallados de esta revisión pueden colaborar para la elaboración de protocolos para el manejo de la anorexia en cuidados paliativos

Are cannabinoids an alternative for cachexia-anorexia syndrome in patients with advanced cancer? / ¿Son los cannabinoides una opción para el síndrome anorexia-caquexia en pacientes con cáncer avanzado?

INTRODUCTION: Cachexia and anorexia are among the most frequent symptoms in patients with cancer. Cannabinoids have been used in patients with advanced cancer; however, their role is still controversial. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified ten systematic reviews including three studies overall, of which two were randomized trials. We concluded it is not clear whether cannabinoids have any positive effect on increasing weight because the certainty of the evidence is very low. They might not have any effect on appetite, and are probably associated to frequent adverse effects.

INTRODUCCIÓN: La caquexia y la anorexia se encuentran dentro de los síntomas más frecuentes en los pacientes oncológicos. Los cannabinoides han sido propuestos para su manejo en los pacientes con cáncer avanzado, sin embargo, su rol es controvertido. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud a nivel mundial, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos diez revisiones sistemáticas, que en conjunto incluyen tres estudios, entre ellos dos ensayos aleatorizados. Concluimos que no está claro si los cannabinoides logran o no un aumento de peso en pacientes con anorexia-caquexia porque la certeza de la evidencia es muy baja, podrían no tener tampoco efecto sobre el apetito, y probablemente se asocian a efectos adversos frecuentes.

Antioxidant effects of açaí seed ( Euterpe oleracea ) in anorexia-cachexia syndrome induced by Walker-256 tumor.

PURPOSE:: To assess antioxidant effects of açaí seed extract on anorexia-cachexia induced by Walker-256 tumor. METHODS:: A population of 20 lab rats were distributed into four groups (n=5): Control Group (CG), which only received tumor inoculation. Experimental Group-100 (EG-100), with animals submitted to tumor inoculation and treated with seed extract in a 100 mg / ml concentration through gavage. Experimental Group-200 (EG-200), with animals submitted to tumor inoculation and treated with seed extract in a 200 mg / ml concentration. Placebo Group (GP), which received tumor inoculation and ethanol-water solution. We analyzed proteolysis, lipid peroxidation, tumor diameter and weight. RESULTS:: Lipid peroxidation was representative only in the cerebral cortex, where there was more oxidative stress in rats treated with the extract (p = 0.0276). For proteolysis, there was less muscle damage in untreated rats (p = 0.0312). Only tumor diameter in treated rats was significantly lower (p = 0.0200) compared to untreated ones. CONCLUSIONS:: The açaí seed extract showed no beneficial effect on the general framework of the cachectic syndrome in lab rats. However, some anticarcinogenic effects were observed in the tumor diameter and weight.

Antioxidant effects of açaí seed ( Euterpe oleracea ) in anorexia-cachexia syndrome induced by Walker-256 tumor

ABSTRACT PURPOSE: To assess antioxidant effects of açaí seed extract on anorexia-cachexia induced by Walker-256 tumor. METHODS: A population of 20 lab rats were distributed into four groups (n=5): Control Group (CG), which only received tumor inoculation. Experimental Group-100 (EG-100), with animals submitted to tumor inoculation and treated with seed extract in a 100 mg / ml concentration through gavage. Experimental Group-200 (EG-200), with animals submitted to tumor inoculation and treated with seed extract in a 200 mg / ml concentration. Placebo Group (GP), which received tumor inoculation and ethanol-water solution. We analyzed proteolysis, lipid peroxidation, tumor diameter and weight. RESULTS: Lipid peroxidation was representative only in the cerebral cortex, where there was more oxidative stress in rats treated with the extract (p = 0.0276). For proteolysis, there was less muscle damage in untreated rats (p = 0.0312). Only tumor diameter in treated rats was significantly lower (p = 0.0200) compared to untreated ones. CONCLUSIONS: The açaí seed extract showed no beneficial effect on the general framework of the cachectic syndrome in lab rats. However, some anticarcinogenic effects were observed in the tumor diameter and weight.

Guarana (Paullinia cupana) Improves Anorexia in Patients with Advanced Cancer.

PURPOSE: Anorexia is prevalent in cancer patients with advanced disease. In this pilot phase II, open label, nonrandomized trial, we evaluated the efficacy and safety of guarana (Paullinia cupana) in patients with cancer and weight loss. METHODS: We included advanced cancer patients with decreased appetite and weight loss of more than 5% from their baseline. All of the patients received 50 mg of the crude dry extract of guarana twice a day for 4 weeks. The trial was designed in two phases (Simon model). We considered a positive response in the first phase to be at least 5% weight gain or a three-point improvement in the appetite scale in at least three of the first 18 evaluable patients. RESULTS: Of the 34 eligible patients, 30 were included and 18 completed the protocol. Only one patient abandoned the protocol due to toxicity (grade II arthralgia). No grade 3 or 4 toxicities and no significant differences in nausea, weight loss, or quality of life (FACT-G) occurred. Only two of the 18 patients who completed the study had weight gain above 5% from their baseline, whereas six patients had at least a 3-point improvement in the visual appetite scale. The M.D. Anderson Symptom Inventory (MDASI) was used to evaluate several symptoms, and we observed a significant decrease in the lack of appetite (p = 0.02) and in somnolence (p = 0.0142). CONCLUSION: We concluded that the weight stabilization and increased appetite that we observed in this study justify further studies of guarana in this patient population.

Nutrition in the last days of life.

PURPOSE OF REVIEW: To summarize current knowledge about nutritional aspects in the final stage of life, with emphasis on mechanisms and clinical diagnosis, ethical aspects and management. RECENT FINDINGS: The most recent advances on the subject include new mechanisms involved in the pathophysiology, use of therapeutic approach combined with n-3 fatty acids and the active intervention of the patient in decision making. SUMMARY: The nutritional deterioration in a patient who passes the last stages of his life constitutes a subject area to varied analysis and considerations. For this reason, there exist an increasing number of investigations, particularly in the areas of pathophysiology and of therapeutics. The aspects related to quality of life, cultural context and bioethics, add more complexity to the subject.

Megestrol acetate for the treatment of anorexia-cachexia syndrome.

BACKGROUND: Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993 MA was approved by the USA's Federal Drug Administration for the treatment of anorexia, cachexia, or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown, and its effectiveness for anorexia and cachexia in neoplastic and AIDS patients is under investigation. OBJECTIVES: To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies. SEARCH STRATEGY: Studies were sought thorough an extensive search of the electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search was carried out on October 2002. SELECTION CRITERIA: Studies were included in the review if they assessed megestrol acetate compared to placebo or other drug treatments in randomized controlled trials of patients with a clinical diagnosis of anorexia-cachexia related to cancer, AIDS or another underlying pathology. DATA COLLECTION AND ANALYSIS: Data extraction was conducted by two independent authors, and methodological quality evaluated. Quantitative analyses were performed using appetite and quality of life as a dichotomous variable, and weight gain was analysed as continuous and dichotomous variables. Studies with more than 50% of patients lost to follow-up were excluded from the analysis. MAIN RESULTS: Thirty trials met the inclusion criteria (4123 patients). Twenty-one trials compared MA at different doses with placebo; four compared different doses of MA versus other drugs; two compared MA with other drugs and placebo; and three compared different doses of MA. For all patient conditions, meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer patients. Analysing quality of life, clinical and statistical heterogeneity was found and discussed. There was insufficient information to define the optimal dose of MA. AUTHORS' CONCLUSIONS: This review demonstrates that MA improves appetite and weight gain in patients with cancer. No overall conclusion about quality of life (QOL) could be drawn due to heterogeneity. The small number of patients, methodological shortcomings and poor reporting have not allowed us to recommend megestrol acetate in AIDS patients or with other underlying pathologies.

[Anorexia nervosa and bulimia nervosa. Psychological considerations for its treatment]. / Anorexia nervosa y bulimia nervosa. Consideraciones psicológicas para su tratamiento.

It is presented the current perspectives in the study and treatment of the eating disorders, in specific: anorexia nervosa and bulimia nervosa, epidemiology, and the interface among the different medical specialties, nutrition and sciences of the behavior, the diagnostic approaches, instruments and current therapeutic models.

Estudo de fase II de acetato de megestrol em anorexia e perda de peso em pacientes com AIDS / Phase II trial of megestrol acetate in patients with Aids-related anorexia and weight loss

Objetivos: Avaliar o efeito da suspensäo oral de acetato de megestrol na alteraçäo de peso corpóreo, na diminuiçäo da anorexia e na melhora da qualidade de vida de pacientes com AIDS. Desenho do Estudo: Estudo aberto, com 600 mg de acetato de megestrol em suspensäo oral, por dia, por 12 semanas. Pacientes: Foram envolvidos no estudo 20 pacientes soropositivos para HIV, estando na faixa de 30 porcento de seu peso ideal e que perderam mais de 10 por cento de seu peso corpóreo inicial desde o diagnóstico da infecçäo por HIV. Resultados: Foram avaliados 20 pacientes soropositivos para HIV, sendo 8 (40 por cento) do sexo feminino, 12 (60 por cento) do sexo masculino, com idade média de 33,7 anos, recebendo 600mg/dia de acetato de megestrol. Antes do uso da medicaçäo do estudo, os pacientes apresentavam peso médio de 55,3 Kg e após o uso da mesma este valor passou a 62,8 Kg com ganho percentual de 13,6 porcento. Conclusöes: A ingestäo do medicamento acetato de megestrol teve grande importância na melhora do estado nutricional dos pacientes, uma vez que a maioria apresentou aumento de apetite e conseqüente aumento de peso sem apresentar intercorrências que pudessem interferir no diagnóstico do seu estado nutricional.

Tumor de pâncreas: tratamento de suporte / Tumor of the pancreas: symptomatic treatment

O carcinoma de pâncreas tem mau prognóstico e curta sobrevida. A despeito dos métodos de diagnóstico avançado, o diagnóstico do tumor de pâncreas é freqüentemente retardado em virtude dos sintomas iniciais serem vagos e näo específicos. O tratamento sintomático, na maioria dos pacientes, é a única forma terapêutica, uma vez que a cura cirúrgica ocorre em percentual inexpressivo dos casos. O manuseio adequado das manifestaçöes clínicas visa melhorar a qualidade de vida e inclui o controle da anorexia e perda de peso, dor abdominal, icterícia secundária a compressäo da via biliar e conseqüências digestivas da cirurgia pancreática. A anorexia freqüentemente acompanha os portadores de cáncer de pâncreas, o que contribui para reduçäo da ingestäo calórica, perda de peso e desnutriçäo. Pacientes impossibilitados de ingestäo adequada, em razäo de obstruçäo do trato intestinal, podem se beneficiar de nutriçäo enteral ou parenteral. Os pacientes con anorexia podem se beneficiar de estratégias farmacológicas recentes. O acetato de megestrol produz melhora do apetite e ganho de peso em grande parte dos portadores de câncer avançado. A icterícia obstrutiva pode ser tratada pela drenagem biliar cirúrgica ou, de maneira paliativa, pelo uso de endoprótese. A drenagem biliar percutânea transhepática ou endoscópica é um método terapêutico eficiente para descompressäo em 80 a 85 por cento dos pacientes com doença em estágio avançado. A dor abdominal deve ser tratada pela administraçäo oral de analgésicos näo narcóticos ou, se necessário, analgésicos narcóticos potentes, e, algumas vezes, pelo bloqueio do plexo celíaco, esplancnicectomia ou radioterapia abdominal. O bloqueio do plexo celíaco com álcool consiste no tratamento específico e paliativo da dor mais utilizado no câncer de pâncreas. Finalmente, as conseqüências digestivas da ressecçäo pancreática säo tratadas com sintomáticos

[Tumor of the pancreas. Support treatment]. / Tumor de pâncreas. Tratamento de suporte.

Carcinoma of the pancreas has a poor prognosis with a short survival time. Despite diagnostic advances, diagnosis is often delayed because early symptoms are frequently vague and non-specific. Symptomatic treatment is the only possibility in the large majority of patients with pancreatic cancer since curative surgical excision of the tumor is only possible in few cases. Symptoms managed, in the aim to improve the quality of life, include weight loss and anorexia, abdominal pain, jaundice secondary to biliary compression and digestives consequences of pancreatic surgery. Anorexia is a frequent complaint in patients with pancreatic cancer, and contributes to decreased caloric intake, weight loss and malnutrition. Patients who are unable to eat, due to obstruction or dysfunctional gastrointestinal tract, may benefit from enteral or parenteral nutrition. Patients whose main reason to not obtain adequate food intake is anorexia may benefit from recently developed pharmacologic strategies. Megestrol acetate often produce an improvement in appetite and weight gain in patients with advanced cancer. Jaundice can be treated by surgical biliary drainage or better still by palliative biliary endoprosthesis. Percutaneous transhepatic or endocopic biliary drainage are now well established methods for decompressing malignant biliary obstruction. Pain occurs in 80-85% of patients with advanced disease. Abdominal pain should be treated by oral non-narcotic analgesics, or, if necessary, potent narcotic analgesics, and sometimes by percutaneous block of the celiac ganglion, splancnicectomy or abdominal radiotherapy. Celiac plexus block with alcohol is the most common and well described therapy for the specific pain from carcinoma of the pancreas. Digestive consequences of pancreatic surgery also require symptomatic treatment.

Anorexia infantil, etiología y tratamiento / Infantile anorexia, etiology and treatment

Se presentan las principales características de un síndrome común en la práctica cotidiana de un pediatra: la anorexia infantil. Se revisa etiología correlacionándola con etapas de crecimiento y desarrollo infantil, destacando asimismo la influencia de los padres que interfieren (con sus deseos, angustias o preocupación exagerada) el satisfactorio cumplimiento de la alimentación. Se consignan recomendaciones prácticas para establecer un diagnóstico cabal, identificar sus causas y peculiaridades, y sugerir a los médicos que atienden niños para que hagan comprender a los padres su importante papel educativo en lo relativo a la alimentación, así como en muchos otros aspectos del desarrollo infantil que de alguna manera se relacionan con ella