Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer.

BACKGROUND: Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy. Results from the final analysis of overall survival have not yet been reported. METHODS: In this double-blind, phase 3 trial, men with nonmetastatic, castration-resistant prostate cancer (defined on the basis of conventional imaging and a PSA doubling time of ≤10 months) who were continuing to receive androgen-deprivation therapy were randomly assigned (in a 2:1 ratio) to receive enzalutamide at a dose of 160 mg or placebo once daily. Overall survival was assessed with a group sequential testing procedure and an O'Brien-Fleming-type alpha-spending function. RESULTS: As of October 15, 2019, a total of 288 of 933 patients (31%) in the enzalutamide group and 178 of 468 (38%) in the placebo group had died. Median overall survival was 67.0 months (95% confidence interval [CI], 64.0 to not reached) in the enzalutamide group and 56.3 months (95% CI, 54.4 to 63.0) in the placebo group (hazard ratio for death, 0.73; 95% CI, 0.61 to 0.89; P = 0.001). The exposure-adjusted rate of adverse events of grade 3 or higher was 17 per 100 patient-years in the enzalutamide group and 20 per 100 patient-years in the placebo group. Adverse events in the enzalutamide group were consistent with those previously reported for enzalutamide; the most frequently reported events were fatigue and musculoskeletal events. CONCLUSIONS: Enzalutamide plus androgen-deprivation therapy resulted in longer median overall survival than placebo plus androgen-deprivation therapy among men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level. The risk of death associated with enzalutamide was 27% lower than with placebo. Adverse events were consistent with the established safety profile of enzalutamide. (Funded by Pfizer and Astellas Pharma; PROSPER ClinicalTrials.gov number, NCT02003924.).

Epidemiological profile of Brazilian oncological patients seen by a reference oncology center of the public health system and who migrate in search of adequate health care

SUMMARY INTRODUCTION Structural disparities between different Brazilian regions in public health system cause patients to migrate in search of better conditions to treat their diseases. Besides patient's discomfort, there is a concentration of care in large centres, causing overload to current capacity. OBJECTIVE To evaluate migratory flow and associated factors in a reference service in oncology. METHODS Cross-sectional study conducted at a referral oncology service in Great ABC region of São Paulo. Patients were interviewed, and clinical and demographic data collected. RESULTS Between March-July 2016, 217 patients were included. Analysis showed a divergence between the postal code registered in the medical record and that recorded during the interview in approximately 10% of cases. Of these, 42.9% were residents of other states. Search for treatment motivated most patients to seek service outside their city. CONCLUSION Results reflect the informal search for medical care outside the home area. Besides the direct impact on patients' quality of life, migratory flow has an economic-social impact because these patients place a burden and impose costs on services of cities where they do not perform their responsibilities as citizens. Confirmation of the existence of a significant migratory flow demonstrates the need to discuss restructuring public health policies.

RESUMO INTRODUÇÃO As disparidades estruturais entre diferentes regiões brasileiras no sistema de saúde pública fazem com que os pacientes migrem em busca de melhores condições para tratar suas doenças. Além do desconforto do paciente, há uma concentração de cuidados em grandes centros, causando sobrecarga da capacidade atual. OBJETIVO Avaliar o fluxo migratório e fatores associados em um serviço de referência em oncologia. MÉTODOS Estudo transversal realizado em um serviço de oncologia de referência na região do Grande ABC, em São Paulo. Os pacientes foram entrevistados e dados clínicos e demográficos coletados. RESULTADOS Entre março e julho de 2016 foram incluídos 217 pacientes. A análise mostrou uma divergência entre o código de endereçamento postal registrado no prontuário médico e o registrado durante a entrevista em aproximadamente 10% dos casos. Desses, 42,9% eram residentes de outros estados. A busca de tratamento motivou a maioria dos pacientes a buscar serviços fora de sua cidade. CONCLUSÃO Os resultados refletem a busca informal de cuidados médicos fora da área de residência. Além do impacto direto na qualidade de vida dos pacientes, o fluxo migratório tem um impacto econômico-social porque esses pacientes colocam um fardo e impõem custos aos serviços das cidades onde não executam suas responsabilidades como cidadãos. A confirmação da existência de um fluxo migratório significativo demonstra a necessidade de discutir a reestruturação das políticas de saúde pública.

Cutaneous side effects of molecularly targeted therapies for the treatment of solid tumors.

BACKGROUND: Currently, molecularly targeted drugs are part of the therapeutic arsenal for the treatment of many neoplasms and are responsible for improvements in the quality of life and survival of patients. Although they act on proteins and components within biochemical pathways that are expressed to a greater extent in neoplastic cells, these drugs can also interfere with the activity of normal cells. SCOPE: This article reviews the cutaneous side effects of main molecularly targeted cancer therapies for solid tumors. FINDINGS: The use of these drugs causes side effects, and the skin is one of the most commonly affected organs. In this literature review, we discuss the adverse cutaneous effects caused by molecularly targeted drugs. CONCLUSION: The identification of these reactions is important to both dermatologists and oncologists so that they properly diagnose the reaction and administer adequate treatment, which would allow greater adherence to the oncological treatment and improve patients' quality of life.

Medical Student Oncology Congress: Designed and Implemented by Brazilian Medical Students.

Oncology is an essential field of medicine; however, its teaching is occasionally underemphasized and uncoordinated during medical school. An alternative method of providing additional oncological information to medical students is through extracurricular activities, such as congresses and medical student associations. The aim of this paper is to describe a Medical Student Oncology Congress entirely designed and organized by medical students. Three medical students from oncology study and research groups identified the gap in oncology training at universities and decided to organize a congress for students. They selected representatives from 26 universities in Brazil for onsite registration and created a website for online registration and promotion of the congress. To determine the topics of the lectures, they searched the medical literature for the most commonly occurring cancers in adults and children. Extrapolating the academic content of oncology, they organized lectures by non-governmental organizations (NGOs), talks on career guidance and research in this field as well as a role-playing workshop to train future doctors on how to deliver news to patients. There were a total of 609 attendees, with 590 students from 26 different universities in Brazil. Approximately 82% were medical students, and among the participants there were also 15 medical educators. A total of 80.75% of the participants were extremely satisfied with the congress, and 99.17% would recommend it to a colleague. Most of the overall cost of the congress, 96%, was covered by registration fees. There was a 6% positive net balance, which was donated to the NGOs participating in the congress. This successful experience proves that it is possible to have a congress fully designed, organized and managed by students. It demonstrates how students can be active participants in their own education, as opposed to a classic approach through which only professors are responsible for instruction.

Epidemiological profile of Brazilian oncological patients seen by a reference oncology center of the public health system and who migrate in search of adequate health care.

INTRODUCTION: Structural disparities between different Brazilian regions in public health system cause patients to migrate in search of better conditions to treat their diseases. Besides patient's discomfort, there is a concentration of care in large centres, causing overload to current capacity. OBJECTIVE: To evaluate migratory flow and associated factors in a reference service in oncology. METHODS: Cross-sectional study conducted at a referral oncology service in Great ABC region of São Paulo. Patients were interviewed, and clinical and demographic data collected. RESULTS: Between March-July 2016, 217 patients were included. Analysis showed a divergence between the postal code registered in the medical record and that recorded during the interview in approximately 10% of cases. Of these, 42.9% were residents of other states. Search for treatment motivated most patients to seek service outside their city. CONCLUSION: Results reflect the informal search for medical care outside the home area. Besides the direct impact on patients' quality of life, migratory flow has an economic-social impact because these patients place a burden and impose costs on services of cities where they do not perform their responsibilities as citizens. Confirmation of the existence of a significant migratory flow demonstrates the need to discuss restructuring public health policies.

"Burnout in Medical Oncology Fellows: a Prospective Multicenter Cohort Study in Brazilian Institutions".

Burnout syndrome is a common occurrence among oncologists. Doctors enrolled in residency programs in clinical oncology are exposed to similar risk factors; however, few data are available in this population. This study assessed the occurrence of burnout and associated factors among first-year residents at Brazilian institutions. The present prospective, multicenter, cohort study was conducted with doctors enrolled in residency programs in clinical oncology at Brazilian institutions affiliated with the public health system. The participants answered a sociodemographic questionnaire, the Maslach Burnout Inventory (MBI), Lipp's Stress Inventory, and the Beck Depression Inventory (BDI), upon admission to the program and 6 and 12 months later. Of 37 eligible residency programs in 2009, 11 (30.6 %) agreed to participate in the study. Fifty-four residents, representing 100 % of new admissions to the participating institutions, were included. Most of the participants met the criteria for severe burnout upon admission to the residency programs (emotional exhaustion in 49.0 % and depersonalization in 64.7 %). The scores on MBI domains emotional exhaustion and depersonalization increased significantly (p < 0.01) during the first year of residency, and the prevalence of burnout increased to 88 % at the end of that first year. The present study found a high prevalence of burnout among doctors enrolled in residency programs in clinical oncology at Brazilian institutions. A large fraction of the participants met the criteria for burnout syndrome upon admission to the program, which suggests that the problem began during the course of the previous residency program in internal medicine.

Entendendo a síndrome de Burnout na Cancerologia / Understanding Burnout syndrome in the of Medical Oncology

Contexto: A síndrome de Burnout é um importante distúrbio psiquiátrico ocupacional resultante do estresse na vida profissional. É caracterizada por exaustão emocional, despersonalização (tratar pacientes e pessoas em geral como se fossem objetos), e sentimentos de baixa realização pessoal. A Oncologia é uma das áreas médicas em que a gravidade da doença dos pacientes, o uso de tratamentos tóxicos e prolongados, e o contato próximo a pacientes terminais e seus familiares podem sujeitar os profissionais da saúde a estresse considerável. Métodos: Os autores revisaram a literatura, a fim de melhor compreender a síndrome de Burnout na área da Cancerologia. Conclusão: A síndrome de Burnout entre os médicos cancerologistas é comum, no entanto, novos estudos de alta qualidade são necessários para identificar possíveis fatores de risco e intervenções que pudessem ser empregadas para minimizar este problema.

Estudo piloto da avaliação do grau de compreensão do termo de consentimento livre e esclarecido por pacientes partícipes em pesquisas oncológicas / Evaluation of understanding grade of the informed consent by subjects in oncology research: a pilot study

Introdução: Com o avanço da tecnologia na área da saúde, a pesquisa em seres humanos cresce a cada dia. O Termo de Consentimento Livre e Esclarecido (TCLE) é um documento que deve ser assinado obrigatoriamente por pacientes que aceitam participar de algum protocolo de pesquisa clínica. A sua compreensão é de extrema importância, nele devem estar contidas todas as informações sobre a pesquisa. Objetivos: Neste estudo avaliamos o grau de compreensão do TCLE pelos pacientes partícipes em pesquisas oncológicas. Avaliamos também os principais pontos e causas da não compreensão do TCLE e a compreensão do termo ?placebo?. Métodos: De janeiro até junho de 2012, todos os pacientes que vieram ao Centro de Estudos e Pesquisas em Hematologia e Oncologia (CEPHO) assinar um TCLE, para qualquer estudo em andamento, foram convidados a preencher dois questionários, sendo o primeiro referente a informações pessoais, motivos para participação na pesquisa e procedimentos de aplicação do TCLE e o segundo no qual o paciente teria que assinalar os itens que encontrou no TCLE. Dentre eles haviam itens falsos que foram usados como controle. Resultados: Um total de 23 pacientes participaram da pesquisa, o grau de compreensão dos pacientes foi de 72,4%, os assuntos menos entendidos foram as alternativas de tratamento para a doença e o termo ?placebo?. Conclusão: A compreensão do TCLE pelos pacientes foi considerada boa, mesmo com o fato de os TCLEs incluírem informações técnicas. Pelos achados deste trabalho se sugere que há necessidade de uma abordagem mais cuidadosa com algumas informações específicas, tais como o termo ?placebo? e as alternativas terapêuticas para a patologia em questão.

Comportamento indolente de um tumor phyllodes maligno metastático para pulmão: relato de caso com sobrevida superior a 11 anos / Indolent behavior of a malignant phyllodes tumor metastatic to the lungs: a case report with overall survival that exceeds 11 years

Tumor phyllodes é uma neoplasia fibroepitelial que corresponde a menos de 0,5% dos cânceres de mama. A doença metastática ocorre em menos de 5% dos casos e a sobrevida mediana é de cerca de 30 meses. Relatamos um caso raro de doença metastática para pulmão, confirmada por biópsia, com evolução extremamente indolente, superando os 11 anos de seguimento. A despeito da indolência do componente metastático, houve recidiva local de crescimento paradoxalmente rápido.

Tegafur-uracil is a safe alternative for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle.

OBJECTIVE: The objective of this study was to evaluate the safety of using tegafur-uracil (UFT) in colorectal cancer patients with partial dihydropyrimidine dehydrogenase (DPD) deficiency. PATIENTS AND METHODS: The study included five colorectal cancer patients who presented with acute toxicity (grades 3 and 4) after being given the first cycle of chemotherapy using 5-fluorouracil. The DPD deficiency was confirmed by gene sequencing. After a full recovery from all side effects, we changed the regimen to UFT (300 mg/m(2)/day) associated with leucovorin (90 mg/day) for 21 days, with an empirical dose reduction of at least 10% in the first cycle. RESULTS: We prospectively analysed 22 UFT cycles in 5 patients. We did not observe any episodes of grade 3 or 4 toxicity. The predominant toxicities were of grades 1 and 2 (nausea, vomiting and diarrhoea). CONCLUSION: Here, we demonstrate a complete absence of severe toxicity in all patients and cycles analysed. We believe that UFT is a safe alternative for the treatment of patients with partial DPD deficiency.

Early switching from morphine to methadone is not improved by acetaminophen in the analgesia of oncologic patients: a prospective, randomized, double-blind, placebo-controlled study.

OBJECTIVES: This study aims to evaluate the efficacy of methadone as substitute for morphine and to investigate if the addition of acetaminophen could reduce the time to attain an equianalgesic dose of methadone and/or to improve the level of pain control in oncologic patients. PATIENTS AND METHODS: Fifty patients on stable doses of morphine for 1 week were switched to methadone using a "stop-start" strategy and randomized in a double-blind fashion to receive either acetaminophen (750 mg PO every 6 hours) or placebo for a 7-day period. We collected data regarding level of pain, side effects, and quality of life. RESULTS: Substitution of morphine for methadone resulted in a significant reduction in constipation (p < 0.001) and xerostomia (p = 0.03). There was also an improvement in the numeric pain scale (p = 0.03) as well as a significant improvement in the functional level and symptomatology according to the QLQ-C30 questionnaire. Addition of acetaminophen did not improve pain control or reduce the time of stabilization of analgesia once methadone was introduced. At the end of the study, most patients (70.8%, p = 0.001) preferred methadone to morphine. CONCLUSIONS: Early switching from morphine to methadone was a safe and efficient strategy for the reduction of side effects and improvement of analgesia, allowing for a comfortable dosing regimen. In this scenario, the association with acetaminophen did not improve pain control or reduce the time to achieve an equianalgesic dose of methadone.