Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial / 中华医学杂志(英文版)

BACKGROUND@#LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.@*METHODS@#We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.@*RESULTS@#On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).@*CONCLUSION@#LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04563936.

Radiomics based on biparametric MRI for the detection of significant residual prostate cancer after androgen deprivation therapy: using whole-mount histopathology as reference standard / 亚洲男科学杂志(英文版)

We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10-3 mm2 s-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10-3 mm2 s-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10-3 mm2 s-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.

Calidad de vida en pacientes con metástasis óseas por cáncer de próstata tratados con ácido zoledrónico / Quality of life in patients suffering from bone metastasis due to prostate cancer treated with zoledronic acid

Introducción: El ácido zoledrónico mejora la calidad de vida en pacientes con metástasis óseas por cáncer prostático. Objetivo: Evaluar la calidad de vida relacionada con la salud con el cuestionario EORTC QLQ-BM22 en pacientes con metástasis óseas por cáncer prostático tratados con ácido zoledrónico. Métodos: Se realizó un estudio prospectivo-descriptivo de 71 pacientes con cáncer prostático metastásico a hueso tratados en el servicio de oncología del Hospital Clínico Quirúrgico "Hermanos Ameijeiras" con: edades 18-80 años, ECOG<3, expectativa de vida >6 meses, y seguimiento de al menos doce meses. Se administró ácido zoledrónico cada 21-28 días. Se aplicó la escala visual análoga y el módulo EORTC QLQ-BM22. Resultados: Los pacientes tenían una mediana de 71 años de edad, Gleason ≥ 8: en 57,7 % de los pacientes, PSA al diagnóstico ≥ 20 ng/mL: 70,4 por ciento, ECOG 1: 67,6 por ciento, y estadio IV como presentación inicial: 50,7 por ciento. Metástasis óseas sin toma visceral: 84,5 por ciento, en vértebras 36,6 por ciento, <3 sitios 66,2 por ciento, y metástasis óseas blásticas 60,6 por ciento. Eventos esqueléticos relacionados previos al ácido zoledrónico 7,9 por ciento (fractura), y posteriores, 5,6 por ciento (radioterapia anti-álgica). A doce meses, acorde a la escala visual análoga, se alcanzó respuesta completa: 71 por ciento, y parcial: 29 por ciento (p<0,05). Luego de la aplicación del módulo EORTC QLQ-BM22, se comprobó disminución significativa tanto en la escala de síntomas como en la funcional, independientemente de otros factores. Conclusiones: Los tratamientos específicos para cáncer prostático combinado a zoledrónico mejoran significativamente el dolor y calidad de vida relacionada con la salud en pacientes con metástasis óseas(AU)

Introduction: Zoledronic Acid improves the quality of life of patients suffering from prostate cancer. Objectives: To assess the health-related quality of life using EORTC QLQ-BM22 questioner in patients suffering from prostate cancer, treated with zoledronic acid. Method: A prospective-descriptive study was carried out in 71 patients suffering from prostate cancer involving bones, with ages ranging between 18 and 80 years, and who were treated in the oncology service at Hermanos Ameijeiras Hospital. The ECOG was less than 3, life expectancy> 6 months, and follow-up of at least twelve months. Zoledronic acid was administered every 21-28 days. The visual analog scale and EORTC QLQ-BM22 module were applied. Results: The patients had median age of 71 years, Gleason ≥ 8: in 57.7% of the patients, PSA at diagnosis ≥ 20 ng / mL: 70.4%, ECOG 1: 67.6 percent, and stage IV as initial presentation: 50.7 percent. Bone metastases without visceral intake: 84.5 percent, in vertebrae 36.6 percent, <3 sites 66.2 percent, and blast bone metastases 60.6 percent. Skeletal events related to zoledronic acid before 7.9 percent (fracture), and after 5.6 percent (anti-allergic radiotherapy). At twelve months, according to the visual analog scale, a complete response was achieved, 71 percent, and a partial response, 29 percent (p <0.05). After the application of EORTC QLQ-BM22 module, a significant decrease was found in both the symptom and functional scales, regardless of other factors. Conclusions: Specific treatments for prostate cancer combined with zoledronic significantly improve pain and health-related quality of life in patients with bone metastases(AU)

Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux

BACKGROUND: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. RESULTS: In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin. CONCLUSIONS: Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic.

Mortality of motorcyclists due to traffic injuries in Brasil: a population-based study in Brazilian capitals

SUMMARY OBJECTIVE: To analyze the mortality trend of young men who were victims of traffic injuries involving motorcycles in all Brazilian capitals from 2001 to 2015. METHODS: A time-series study on all deaths of men aged 20-39 years old due to traffic injuries involving motorcycles in all 27 Brazilian capitals. We used the joinpoint regression model for temporal analysis and calculated the Annual Percent Change (APC) and Average Annual Percent Change (AAPC) to verify the mortality trends. RESULTS: A total of 12,058 deaths of young men were recorded in the Brazilian capitals during the period studied. The highest mortality rates were observed in Boa Vista/Roraima (34.0/100,000 population) and Palmas/Tocantins (29.80/100,000). Twelve of the 27 capitals showed an increasing trend in mortality, with the highest percentage increase being observed in Salvador (APC: 29.0%) and São Paulo (APC: 13.1%). None of the capitals showed a decline in the trend of mortality. CONCLUSIONS: Overall, the mortality of young men from traffic injuries involving motorcycles shows an increasing trend in 12 of the 27 capitals, which represents a public health problem that requires the implementation of more effective public policies.

RESUMO OBJETIVO: Analisar a tendência temporal da mortalidade de homens jovens vítimas de acidente de trânsito envolvendo motocicletas em todas as capitais brasileiras de 2001 a 2015. MÉTODOS: Estudo de séries temporais incluindo as mortes de homens de 20 a 39 anos por lesões no trânsito envolvendo motocicletas nas 27 capitais brasileiras. Para a análise, foi utilizado o modelo de regressão do ponto de inflexão e calculada a Variação Percentual Anual (APC) e a Variação Percentual Anual Média (AAPC). RESULTADOS: Foram registradas 12.058 mortes de homens jovens nas capitais brasileiras durante o período estudado. As maiores taxas de mortalidade foram observadas em Boa Vista/Roraima (34,0/100.000 habitantes) e Palmas/Tocantins (29,80/100.000). Doze capitais apresentaram tendência crescente de mortalidade, sendo o maior aumento percentual em Salvador (APC: 29,0%) e São Paulo (APC: 13,1%). Nenhuma das capitais mostrou declínio nas taxas. CONCLUSÕES: A mortalidade de jovens por lesões no trânsito envolvendo motocicletas tem mostrado uma tendência crescente em 12 capitais, o que representa um problema de saúde pública que requer a implementação de políticas públicas mais eficazes.

Immunotherapy with PD-1 and PD-L1 inhibitors for prostate cancer / 中华男科学杂志

Prostate cancer (PCa) has become one of the common malignant diseases in elderly men, and its incidence is increasing year by year. Apart from surgery, radiotherapy and chemotherapy, immunotherapy, as with the programmed death receptor-1 (PD-1) or the programmed death ligand-1 (PD-L1) inhibitor, is a most promising new strategy for the treatment of PCa. PD-1 and PD-L1 inhibitors restore the activity of T cells by blocking the PD-1/PD-L1 signaling pathway in tumor cells, reverse the mechanism of tumor immune escape, recover the immune system and directly kill tumor cells. This review focuses on the current progress in the studies of PD-1 and PD-L1 inhibitors in the treatment of PCa.

Identifying quality of life indicators to improve outpatient pharmacy services for prostate cancer patients: a comparison between brazilian and british experiences

ABSTRACT Objectives: Prostate cancer is the most common and fatal cancer amongst Brazilian males. The quality of prostate cancer care in Brazil was systematically reviewed and compared to United Kingdom (UK) National Institute for Health and Care Excellence (NICE) guidelines, which are considered an international benchmark in care, to deter- mine any treatment gaps in Brazilian practice. Materials and Methods: A systematic review of Brazilian and UK literature was under- taken. Additionally, quality of life scores was measured using a FACT-P questionnaire of 36 prostate cancer patients attending the Farmácia Universitária da Universidade de São Paulo (FARMUSP). These scores were compared against NICE care measures for patient safety, clinical efficacy and quality of life indicators determined by either quantitative or qualitative methods. Key findings: The quality of prostate cancer care in Brazil was considered good when compared to NICE guidelines. However, FACT-P data strongly indicated a poor under- standing of treatment received by Brazilian patients and that their mental health needs were not being met. Conclusions: NICE quality statements that address the holistic needs of patients should be implemented into Brazilian outpatient care plans. Addressing the non-medical concerns of patients may improve quality of life and can be easily rolled-out through existing Brazilian pharmacy services at no financial cost to the Brazilian Unified Health System (SUS).

Supposed pituitary-production of human chorionic Gonadotropin induced by androgen deprivation therapy

ABSTRACT Introduction: The main cause of slightly elevated human chorionic gonadotropin (HCG) after successful treatment of male germ cell tumors is considered to be pituitary-derived HCG. It is well known that pituitary-derived HCG is frequently detected in postmenopausal women. We evaluated the status of serum HCG in men with elevated gonadotropins, which were induced by androgen deprivation therapy, using commercially available assays. Materials and Methods: We enrolled 44 patients with prostate cancer, who underwent luteinizing-hormone releasing hormone agonist treatment. We measured serum follicle-stimulating hormone (FSH), serum luteinizing hormone (LH), serum total HCG, serum free HCG-β subunit, and urine total HCG 3 times per patient, on the day of treatment initiation, the next day, and 3 months after. Results: On the day after treatment initiation, serum and urine HCG was detected in 61% and 73% of patients, respectively. Markedly strong correlations were observed between serum/urine HCG and FSH/LH. In particular, receiver operating characteristic curve analysis indicated excellent area under the curve (0.977, 95% confidence interval 0.951-1.003)) for serum HCG-detectable LH. At the cutoff value of 21.07 mIU/mL for serum HCG-detectable LH, the sensitivity and specificity were 96.7% and 95.3%, respectively. Serum HCG-β was not detectable at any times in any patients. Conclusions: Suggested pituitary-derived HCG can be frequently detected in patients with elevated gonadotropins, and there is a firm association between HCG detection and gonadotropin levels.

Una sola tableta de Abiraterona con comida en vez de 4 tabletas en ayuno para pacientes con cáncer de próstata metastásico resistente a la castración: perspectivas fármaco-económicas en un país en desarrollo / One Pill of Abiraterone with Food Instead of Four Pills in Fasting State for Metastatic Castration Resistant Prostate Cancer Patients: Pharmaco-economic Perspectives in a Developing Country

Recientemente se publicó en el Journal of Clinical Oncology un estudio prospectivo aleatorizado fase II, que comparó dosis bajas de Abiraterona (250mg) administrada con comida vs la dosis estándar de dicho medicamento (1000mg), en pacientes con cáncer de próstata metastásico resistente a la castración (mCRPC)1 y concluyó que la dosis baja no es inferior a la dosis estándar en cuanto a la respuesta de PSA y a la supervivencia libre de progresión (PFS).

A prospective randomized phase II study comparing low dose Abiraterone (250 mg) administered with food versus the standard dose (1000 mg) in metastatic castration resistant prostate cancer, was recently published in The Journal of Clinical Oncology. It concluded that the low dose was non-inferior compared to the standard dose for the endpoints prostate specific antigen (PSA) response and progression free survival (PFS).

Cost-effectiveness analysis of abiraterone, docetaxel or placebo plus androgen deprivation therapy for hormone-sensitive advanced prostate cancer / Análise de custo-efetividade da adição de abiraterona ou quimioterapia ao tratamento do câncer de próstata metastático hormônio-sensível

ABSTRACT Objective To evaluate the cost-effectiveness of the addition of chemotherapy or abiraterone to androgen deprivation. Methods We developed an analytical model to determine the cost-effectiveness of the addition of docetaxel or abiraterone versus androgen deprivation therapy alone. Direct and indirect costs were included in the model. The effects were expressed in Quality-Adjusted Life Years adjusted for side effects. Results Compared to androgen deprivation therapy alone, the addition of chemotherapy and of abiraterone generated 0.492 and 0.999, respectively, in Quality-Adjusted Life Years. Abiraterone led to a Quality-Adjusted Life Years gain of 0.506 compared to docetaxel. The incremental costs per Quality-Adjusted Life Years were R$ 133.649,22 for docetaxel, R$ 330.828,70 for abiraterone and R$ 571.379,42 for abiraterone compared to docetaxel, respectively. Conclusion The addition of chemotherapy to androgen deprivation therapy is more cost-effective than the addition of abiraterone to androgen deprivation therapy. However, discounts on abiraterone cost might improve cost-effectiveness.

RESUMO Objetivo Avaliar a relação custo-efetividade da adição de quimioterapia ou abiraterona à terapia de privação hormonal. Métodos Um modelo analítico foi desenvolvido para determinar a relação custo-efetividade da adição de docetaxel ou abiraterona comparada à terapia de privação hormonal isolada. Custos diretos e indiretos foram incluídos no modelo. Os efeitos foram expressos em Anos de Vida Ajustados para Qualidade corrigidos pelos efeitos colaterais de cada terapia. Resultados A adição de quimioterapia e de abiraterona à terapia de privação hormonal aumentou os Anos de Vida Ajustados para Qualidade em 0,492 e 0,999, respectivamente, em comparação à terapia de privação hormonal isolada. A abiraterona promoveu ganho de Anos de Vida Ajustados para Qualidade de 0,506 em relação ao docetaxel. O custo incremental por Anos de Vida Ajustados para Qualidade foi R$ 133.649,22 para o docetaxel, R$ 330.828,70 para a abiraterona e R$ 571.379,42 para a abiraterona comparada ao docetaxel. Conclusão A adição de quimioterapia à terapia de privação hormonal é mais custo-efetiva que a adição de abiraterona à terapia de privação hormonal. Contudo, descontos no custo da abiraterona poderiam tornar esse tratamento mais custo-efetivo.

Avaliação da segurança e eficácia da abiraterona e enzalutamida pré e pós-quimioterapia no tratamento de pacientes com câncer de próstata metastático castração-resistente: revisão sistemática / Assessment of safety and treatment capacity and pre-treatment and post-treatment chemotherapy without treatment of patients with castration-resistant metastatic prostate cancer: systematic review

O câncer de próstata é no mundo e no Brasil. Alguns pacientes são diagnosticados em fase avançada um problema de saúde pública com alta prevalência ou progridem para tal após o tratamento inicial. Na fase do câncer de próstata metastático castração resistente (CPMCR), o emprego do acetato de abiraterona (AA) e enzalutamida (ENZ) surgem como alternativas de tratamento. O objetivo da tese foi sintetizar as evidências científicas disponíveis, através de uma revisão sistemática (RS), sobre a segurança e eficácia do AA e ENZ empregados em homens com CPMCR antes e após a quimioterapia. Procurou-se também avaliar os mesmos atributos das tecnologias em idosos com idade ≥ 75 anos e pacientes com metástase visceral. Foram pesquisadas cinco bases de dados bibliográficas eletrônicas ­ Medline, Embase, Lilacs, Scopus, Web of Science ­ e duas bases de registros de ensaios clínicos - CENTRAL e ClinicalTrials. Foram utilizados descritores do Medical Subject Headings (MeSH) e termos livres correspondentes ao problema de saúde e às tecnologias de interesse, combinados com uso dos operadores booleanos AND e OR, sem restrição inicial de idioma. Foram incluídos artigos no período de janeiro de 2006 a dezembro de 2018. Todas as etapas da RS foram realizadas por dois revisores independentes. A qualidade metodológica foi avaliada utilizando-se a ferramenta da Colaboração Cochrane. Foram identificadas 9.465 referências, sendo que apenas 29 artigos seguiram para fase de análise dos textos completos. Na segunda fase, apenas 12 estudos foram incluídos, com seis correspondentes a ensaios clínicos fase III originais, quatro contemplando o uso da AA (dois utilizando AA antes da QT e outros dois após-QT) e dois com utilização de ENZ (um antes da QT e um após a QT). Outros seis estudos trataram da análise de subgrupos, idade > 75 anos e com presença de metástase visceral. A sobrevida global e o tempo livre de progressão radiológica mostraram resultados favoráveis ao uso de AA e ENZ, inclusive em indivíduos na faixa etária com mais de 75 anos e com presença de metástase visceral com ganho de sobrevida de aproximadamente quatro meses. Os medicamentos evidenciaram baixas taxas de eventos adversos de graus moderados e graves, não havendo diferença estatística em relação ao uso do placebo em relação a eventos adversos grau V (entre 3,5 e 3,7%), e na taxa de descontinuidade do tratamento, ao redor de 6 a 8%. Ambos os medicamentos AA e ENZ evidenciaram benefícios similares. A despeito dos resultados favoráveis, estes apoiam-se em poucos ECCR fase III, o que deve ser levado em conta em decisões de eventual incorporação ao Sistema Único de Saúde

Prostate cancer is a public health problem with high prevalence worldwide and in Brazil. Some patients are diagnosed at an advanced stage or progress to it after initial treatment. In the phase of castration resistant metastatic prostate cancer (CPMCR), the use of abiraterone acetate (AA) and enzalutamide (ENZ) appear as treatment alternatives. The aim of the thesis was to synthesize the available scientific evidence through a systematic review (SR) on the safety and efficacy of AA and ENZ employed in men with CPMCR before and after chemotherapy (QT). We also sought to evaluate the same attributes of technologies in the elderly aged ≥ 75 years and patients with visceral metastasis. We searched five electronic bibliographic databases - Medline, Embase, Lilacs, Scopus, Web of Science - and two clinical trial record databases - CENTRAL and ClinicalTrials. Medical Subject Headings (MeSH) descriptors and free terms corresponding to the health problem and the technologies of interest were used, combined with the use of AND and OR boolean operators, without initial language restriction. Articles were included from January 2006 to December 2018. All stages of RS were performed by two independent reviewers. Methodological quality was assessed using the Cochrane Collaboration tool. 9,465 references were identified, and only 29 articles went to the full text analysis phase. In the second phase, only 12 studies were included, with six corresponding to original phase III clinical trials, four contemplating the use of AA (two using AA before QT and two after QT) and two using ENZ (one before QT and one after QT). Another six studies dealt with subgroup analysis, age> 75 years and visceral metastasis. Overall survival and time-free radiological progression showed favorable results for the use of AA and ENZ, even in individuals over 75 years of age and visceral metastasis with a survival gain of approximately four months. The drugs showed low rates of moderate and severe adverse events, with no statistical difference regarding placebo use compared to grade V adverse events (between 3.5 and 3.7%), and treatment discontinuation rate. , around 6 to 8%. Both AA and ENZ drugs showed similar benefits. Despite the favorable results, they are supported by few phase III ECCRs, which should be taken into account in decisions of eventual incorporation into the Unified Health System

The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia

ABSTRACT Purpose We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. Materials and Methods We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. Results Among 195 (35.4%) patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001), Gleason score distribution (p<0.001), and number of positive biopsy cores (p<0.002) between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001). Moreover, increasing duration of metformin assumption (≥2 years) was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. Conclusions This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

Cost effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer / Custo-efetividade da adição de quimioterapia ao tratamento hormonal do câncer de próstata metastático sensível a hormônio ou localizado de alto risco

ABSTRACT Objective To assess the cost-effectiveness of chemohormonal therapy in patients with metastatic hormone-sensitive and non-metastatic high-risk prostate cancer. Methods An analytical decision model was developed to determine the cost-effectiveness of chemohormonal therapy versus androgen deprivation therapy alone in patients with metastatic hormone-sensitive prostate cancer and patients with non-metastatic high-risk prostate cancer. The cost-effectiveness in metastatic patients with a high-volume disease was assessed separately. The model used data from randomized clinical trials and drug acquisition costs in Brazil. In addition, the costs of post-progression therapies have been included in this model. The benefits to health are expressed as the quality-adjusted life-years, and the incremental cost-effectiveness ratios were calculated. Results Chemohormonal therapy may be associated with improved quality-adjusted life-years for all patient. The improvement was more than six times greater for patients with high-volume metastatic disease. In these patients, the incremental cost-effectiveness ratios were up to 74% lower than the incremental cost-effectiveness ratios of patients with non-metastatic disease. Conclusion Chemohormonal therapy has been more cost-effective in patients with high-volume metastatic disease.

RESUMO Objetivo Avaliar a relação custo-efetividade da adição de quimioterapia hormonal em pacientes com câncer de próstata metastático sensível a hormônio ou localizado de alto risco. Métodos Um modelo de decisão analítico foi desenvolvido para determinar o custo-efetividade da adição de quimioterapia versus a monoterapia de privação de andrógeno para pacientes com câncer de próstata metastático hormônio-sensível e pacientes de alto risco com câncer de próstata não metastático. O custo-efetividade em pacientes metastáticos com um alto volume da doença foi verificado isoladamente. Os dados do modelo foram obtidos de ensaios clínicos randomizados utilizando custos de aquisição de medicamentos no Brasil. Os custos de terapias pós-progressão também foram incluídos no modelo. Os efeitos foram expressos em anos de vida ajustados por qualidade, e foram calculadas as razões de custo-efetividade incremental. Resultados A adição de quimioterapia levou a um ganho de anos de vida ajustados por qualidade para todos os doentes. Este incremento foi seis vezes maior para os pacientes com doença metastática de alto volume. Nestes pacientes, as taxas do custo incremental por anos de vida ajustados por qualidade foram até 74% mais baixos do que o aumento das taxas dos pacientes com doença não metastática. Conclusão A adição de quimioterapia foi mais custo-efetiva para pacientes com doença metastática de alto volume.

Informe de evaluación científica basada en la evidencia disponible: cáncer de próstata / Scientific evaluation report based on available evidence: prostate cancer

INTRODUCCIÓN: El cáncer de próstata es uno de los tumores sólidos más frecuentes en hombres en el mundo, siendo el más incidente en Europa con una tasa de 214 casos por cada 1000 hombres, superando al cáncer de pulmón y colorrectal. En Chile, el cáncer de próstata se ubica como la segunda causa de muerte por cáncer en hombres, siendo superado sólo por el cáncer de estómago, pero a diferencia de éste, el cáncer de próstata ha tenido una tendencia al alza en las últimas décadas. En efecto, se estima una tasa de mortalidad ajustada de 17,82 varones por 100.000 habitantes el año 2010, lo que se traduce en 1.924 muertes por cáncer de próstata en ese mismo año, ubicándose también como la primera causa de muerte por cáncer en mayores de 80 años en este período. Este informe evalúa abiraterona y enzalutamida para pacientes con cáncer de próstata metastásico que hayan sido sometidos a castración previa, con (segunda línea) o sin el uso de quimioterapia como segunda línea (tercera línea). TECNOLOGÍAS SANITARIAS EVALUADAS: Acetato de Abiraterona y Enzalutamida. EFICACIA DE LOS TRATAMIENTOS: Se encontraron 13 revisiones sistemáticas que incluyen 3 ensayos clínicos aleatorizados de abiraterona y 2 en enzalutamida en pacientes con cáncer de próstata metastásico/avanzado. En pacientes con cáncer de próstata resistente a castración que no han sido previamente tratados con quimioterapia (segunda línea), la abiraterona disminuye la mortalidad, no obstante que probablemente se asocie a un aumento de los efectos adversos. El tratamiento tiene el mismo comportamiento (disminuye la mortalidad y probablemente aumenta efectos adversos) en pacientes que hayan sido previamente tratados con quimioterapia (tercera línea). La enzalutamida disminuye la mortalidad en pacientes con cáncer de próstata resistente a castración que no han sido previamente tratados con quimioterapia (segunda línea), mientras que aumenta los efectos adversos. En el caso de pacientes que han sido previamente tratados con quimioterapia (tercera línea), la enzalutamida disminuye la mortalidad y probablemente aumenta los efectos adversos sérios. ANÁLISIS ECONÓMICO: Se encontraron evaluaciones económicas que comparaban abiraterona con el tratamiento estándar, o abiraterona con enzalutamida. En países como Estados Unidos, Reino Unido, Canadá se consideró que la abiraterona no era costo-efectivo cuando se comparaba con el tratamiento estándar o con enzalutamida, dado su alto costo. Por otra parte, países como República Dominicana, Costa Rica y Panamá consideraron a la abiraterona como costo ahorrativa cuando se comparaba con cabazitaxel más prednisona. Sin embargo, estos países no reportan su umbral de pago. En Brasil y Estados Unidos un análisis de costos mostró que el uso de abiraterona al compararla con enzalutamida estuvo asociada a un menor costo por mes de sobrevida. No se encontraron evaluaciones económicas que hayan evaluado la costo-efectividad de la enzalutamida en pacientes con cáncer de próstata avanzado/metastásico en países de América Latina. En el resto del mundo, aquellos que la consideraron una opción costo efectiva fueron al considerar un costo mensual de tratamiento similar al de la abiraterona. En países como Australia, Alemania, Canadá, Estados Unidos, Francia e Inglaterra recomiendan el uso de abiraterona en combinación con corticoides. Enzalutamida también lo recomiendan aunque alguno de ellos restringe su uso para aquellos pacientes que no utilizaron abiraterona previamente, o tras un acuerdo de precios. El impacto presupuestario estimado para el año 2018 fue de MM $10.131 (abiraterona) y MM $12.316 (enzalutamida) para pacientes que no han recibido previamente quimioterapia (segunda línea), y de MM$ 2.263 (abiraterona) y $MM 2.751 (enzalutamida) en pacientes que si recibieron quimioterapia de manera previa (tercera línea). CONCLUSIÓN: Para dar cumplimiento al artículo 28° del Reglamento que establece el proceso destinado a determinar los diagnósticos y tratamientos de alto costo con Sistema de Protección Financiera, según lo establecido en los artículos 7°y 8° de la ley N°20.850, aprobado por el decreto N°13 del Ministerio de Salud, se concluye que el presente informe de evaluación se considera favorable, de acuerdo a lo establecido en el Título III. de las Evaluaciones Favorables de la Norma Técnica N° 0192 de este mismo ministerio.

Neumonía intersticial inducida por bloqueo androgénico máximo como tratamiento de cáncer de próstata avanzado: Report of one case / Fatal interstitial lung disease associated with maximum androgen blockade

Maximum androgen blockade is the standard endocrine treatment for advanced prostate cancer. Interstitial lung disease in different degrees of severity, with low mortality and excellent response to treatment may appear with its use. We report a 77 years old patient with advanced prostate cancer who developed severe and progressive respiratory failure associated to bilateral pulmonary infiltrates, attributed to the direct effect of maximum androgen blockade. Despite the therapeutic efforts, the patient died. Lung pathology revealed Usual Interstitial Pneumonia.