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Metastatic castrate-resistant prostate cancer (mCRPC) is the last stage of prostate cancer. Although new hormonal agents and taxane-based chemotherapies occurred for mCRPC treatment, the overall survival of mCRPC patients is limited. Olaparib is an inhibitor of poly ADP-ribose polymerase (PARP), which has a key role in DNA damage response. It has been approved for ovarian cancer and breast cancer treatment. PROfound, a phase III clinical trial of olaparib in mCRPC treatment, has been reported in 2019 ESMO and 2020 ASCO-GU. In this paper, we will bring the results and updates of PROfound.
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Objetivo: Estimar os custos do tratamento de pacientes com câncer de próstata não metastático resistente à castração (nmCRPC) e metastático resistente à castração (mCRPC) no Sistema de Saúde Suplementar brasileiro. Métodos: Foi realizada uma busca na literatura para avaliar os dados já disponíveis do custo do tratamento do câncer de próstata no Brasil. Como os dados são escassos, optou-se por utilizar a técnica Delphi com seis médicos oncologistas para levantamento do uso dos recursos. O painel Delphi contou com três etapas, sendo duas on-line e uma presencial, abordando recursos, frequência e porcentagem de uso de exames de imagem e laboratoriais, e dados hospitalares (consultas, pronto-socorro, internações clínica, cirúrgica e em unidade de terapia intensiva). Também foram solicitados dados de padrões de tratamento do câncer de próstata. Por fim, dados do manejo das metástases foram requeridos. Por meio das informações coletadas, foi desenvolvido o microcusteio do câncer de próstata resistente à castração na perspectiva do Sistema de Saúde Suplementar. Resultados: O custo total de tratamento da jornada do paciente com câncer de próstata resistente à castração foi igual a 480.497,25 BRL, e o tratamento unicamente da doença não metastática foi de 189.832,79 BRL e o da doença metastática, de 290.664,46 BRL. Conclusão: Os custos do tratamento de câncer de próstata metastático são substancialmente superiores aos custos do tratamento do paciente não metastático resistente à castração de alto risco, o que parece justificar economicamente o uso de medidas que previnam ou adiem o surgimento de metástases.
Objective: To estimate the treatment costs for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-resistant prostate cancer (mCRPC) within the Brazilian private healthcare system. Methods: A literature search was performed to obtain currently available data on prostate cancer treatment costs in Brazil. As national data are scarce, a Delphi method with a specialist board was chosen with six oncologists for resource estimations. The Delphi panel had three steps: two online and one in-person, addressing what resources, frequencies, and percentages of use of imaging and laboratory exams, hospital data (including medical appointments, emergency room, hospitalizations - clinical, surgical and Intensive Care Unit). Data on prostate cancer treatment patterns were also requested. Finally, metastasis management data was required. Using the collected data, we developed a micro-costing model of castration-resistant prostate cancer in Brazil. Results: The total cost for the entire castration-resistant prostate cancer patient journey was 480.497,25 BRL, with the non-metastatic disease alone costing 189.832,79 BRL and the metastatic disease costing 290.664,46 BRL. Conclusion: The costs of treating metastatic prostate cancer are substantially higher than the treatment of high-risk castration-resistant non-metastatic patients, which seems to economically justify the use of measures that prevent or postpone metastasis.
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Humanos , Costos de la Atención en Salud , Salud Complementaria , Neoplasias de la Próstata Resistentes a la Castración , Metástasis de la NeoplasiaRESUMEN
Background and purpose: Docetaxel plus prednisone chemotherapy can improve the patients' survival for castrate-resistant prostate cancer. Angiogenesis inhibitors can also inhibit the growth of tumor. The curative effect of combined treatment is still not clear. This study aimed to evaluate the efficacy of docetaxel plus prednisone combined with thalidomide in treating castrate-resistant prostate cancer (CRPC) patients with bone metastasis. Methods:A total number of 78 CRPC patients were selected in Fuzhou General Hospital from Dec. 2008 to Jun. 2015. Seventy-eight patients were divided into two groups: 40 patients in chemotherapy group (docetaxel plus prednisone) and 38 patients in combined treatment group (docetaxel plus prednisone combined with thalidomide). A total number of 78 subjects were evaluated by the effective rate, the remission rate of bone pain, the prostate specific antigen (PSA) progression-free surviv-al, the overall survival and adverse effect. Results: The response rate (65.79%) and the remission rate of bone pain (86.84%) in combined treatment group were both higher than those in chemotherapy group (40.00% and 60.00%, P0.05). The rates of adverse effects including peripheral neuritis and lethargy in combined treatment group (26.32% and 55.26%) were higher than those in chemotherapy group (5.00% and 17.50%, P<0.05). Conclusion: Thalidomide combined with docetaxel plus prednisone in CRPC patients with bone metastasis can prolong the PSA progression-free survival and overall survival. The adverse effects are mild. It may become a new choice of treatment for CRPC.
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Objective To explore the prognostic value of modified Glasgow prognostic score (mGPS) and risk factors in predicting overall survival (OS) in the castrate-resistant prostate cancer (CRPC) treated with docetaxel-based chemotherapy.Methods We retrospectively analyzed the data of 48 consecutive Chinese patients with CRPC received docetaxel-based chemotherapy in our institution from January 2008 to January 2012.Patients were divided into three groups according to the mGPS:0,1 and 2 score groups,and compare the OS among the three groups.Variables that were influenced the efficacy of chemotherapy were included in the univariate analysis and multivariate model.Survival analysis was performed using Kaplan-Meier curves,and the differences in overall survival rates were assessed using the Logrank test.Results The follow-up was performed until April 2014.There were 48 CRPC patients including mGPS 0 score group 30 cases,mGPS 1 score group 11 cases and mGPS 2 score 7 cases.The median OS was 22,11,9 months,respectively,P＜0.01.Univariate analysis showed that:prechemotherapy baseline total prostate-specific antigen (tPSA),Eastern Cooperative Oncology Group (ECOG) score,the number of chemotherapy cycle,visceral metastasis and PSA response were associated with poor prognosis (P＜0.05).Multivariate analysis showed that:prechemotherapy mGPS 1-2 score,baseline tPSA＞60 μg/L,the number of cycles of chemotherapy≤5,with visceral metastasis and PSA response in patients with CRPC were independent risk factors for prognosis in the CRPC treated with docetaxel-based chemotherapy.Conclusion mGPS is an independent risk factor for prognosis in the CRPC patients treated with docetaxel-based chemotherapy.
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Polo-like kinase 1 (PLK1) is a highly conserved serine/threonine protein kinase that has attracted research attention be-cause it plays a critical role in mitosis regulation. PLK1 is overexpressed in 80%of human tumors, which indicates a poor prognosis in most tumors. PLK1 is one of the most promising targets for antitumor therapy because it is upregulated in castrate-resistant prostate can-cer (CRPC). This review focused on the basic structure and function of PLK1, the relationship between PLK1 and CRPC occurrence and progression, and CRPC treatment by inhibiting PLK1. This study provides a theoretical basis for the targeted molecular therapy of CRPC.
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Objective To investigate the risk factors for castrate-resistant prostate cancer (CRPC) after prostate cancer treated with androgen deprivation therapy (ADT) within 1 year.Methods One hundred and thirty-one prostate cancer patients treated with ADT in our institute between Jan.2008 and Jan.2011 were selected for this study.Patients were followed up by telephone or in clinic,including serum testosterone,serum PSA,clinical symptoms,imaging studies,digital rectal examination (DRE),survival data,PSA nadir,time to PSA nadir and et al.We mainly studied the CRPC after prostate cancer treated with ADT within 1 year.In the 131 patients,the median age was 70 (ranged from 44-89) years.There were 13 patients (9.9％) less than 60 years,43 patients (32.8％) between 60 and 69 years,62 patients (47.3％) between 70 and 79 years,13 patients (9.9％) more than 80 years.The average body mass index (BMI) was 23.0 (ranged from 14.4-34.4) kg/m2.There were 10 patients less than 18.5 kg/m2,77 patients between 18.5 and 24.0 kg/m2,34 patients between 24.1 and 28.0 kg/m2,and 10 patients more than 28.0 kg/m2.The initial PSA was between 0.3 and 4 707.0 μg/L,there were 19 patients (14.5％) less than 20 μg/L,45 patients (34.4％) between 20 and 99 μg/L,67 patients (51.1％) more than 100 μg/L.One patient (0.7％) was in T1,39 patients (29.8％) in T2,59 patients (45.0％) in T3,32 patients (24.4％) in T4.5 patients (3.8％) were with Gleason score 4,13 patients (9.9％) were with Gleason score 5,24 patients (18.3％) were with Gleason score 6,51 patients (38.9％) were with Gleason score 7,26 patients (19.8％) were with Gleason score 8,9 patients (6.9％) were with Gleason score 9,3 patients (2.3％) were with Gleason score 10.Results There were 32 of 131 patients (24.4％) progressed to CRPC after treated with ADT within 1 year.In the CRPC group,there were 3 patients less than 60 years,15 patients between 60 and 69 years,12 patients between 70 and 79 years,2 patients more than 79 years; 3 patients were less than 18.5 kg/m2,19 patients were between 18.5 and 24.0 kg/m2,7 patients were between 24.0 and 28.0 kg/m2,3 patients were more than 28.0 kg/m2 ; 4 patients were less than 20 μg/L,6 patients were between 20 and 100 μg/L,22 patients were more than 100 μg/L; 4 patients were in T2,13 patients were in T3,15 patients were in T4; 2 patients were with Gleason score 6,11 patients were with Gleason score 7,11 patients were with Gleason score 8,6 patients were with Gleason score 9,2 patients were with Gleason score 10; 29 patients were with metastasis,3 patients without metastasis.Clinical stage (P =0.001),Gleason score (P＜0.001) and metastasis (P=0.011) were statistically significant between the CRPC within 1 year group and the rest group.Conclusions The clinical stage and Gleason score are the risk factors of CRPC treated with ADT within 1 year.The higher of the clinical stage and Gleason score,the greater risk to be the CRPC within 1 year.
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AIM: To evaluate the effects of total flavonoid of chrysanthemum on the expressions of Fas and FasL in male rabbits with dry eye, and to investigate the therapeutic effects of the total flavonoid of chrysanthemum on dry eye. METHODS: Totally 150 male Japanses white rabbits were divided into blank group ( group A ) , sham -operated group ( group B ) , model group ( group C ) , androgen control treatment group (group D), and total flavonoid of chrysanthemum treatment group ( group E ) . The dry eye model was established with orchiectomy on group C, D and E. Rabbits in group E were treated with total flavonoid of chrysanthemum. Rabbits in group D were treated with androgen intramuscular injection. Rabbits in the group A, group B, group C was treated with normal saline. All rabbits were detected with Schirmer's Ⅰ test and tear break-up time (BUT). Fas, FasL were checked on immunohistochemistry. RESULTS:The Schirmer's I test values of group E was significantly higher than that of group C ( P CONCLUSION:The main component of chrysanthemum is flavonoid, which could significantly inhibit happening of dry eye in rabbit after androgen level lowered and lacrimal gland apoptosis and keep basic tears secretory volume and tear film stability.
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AIM: To evaluate the effects of the extract of Buddleja officinalis eye drops in basic tears secretory volume, tear film stability, expression of androgen receptors(AR) in castrated rats with dry eye, and to investigate the therapeutic effects of extract of Buddleja officinalis on dry eye caused by gonadal hormones level imbalance. METHODS:A total of 45 Wistar masculinity rats were divided at random into 9 groups, including normal group(A1,A2 and A3), model group(B1,B2 and B3), therapy group with extract of Buddleja officinalis eye drops(C1,C2 and C3). The "1" stood for being fed for 1 month, and "2" for 2 months, and "3" for 3 months. The dry eye model was established with orchiectomy on group B,C. Group C was treated with Buddleja officinalis extract eye drops for one month. All rats were checked with Schirmer Ⅰ test (SⅠt) and tear film break-up time (BUT). Expression of AR was analyzed by flow cytometer(FCM). RESULTS:The SⅠt value of group C was significantly higher than that of group B (P<0.01) and the BUT value of group C was significantly longer than that of group B (P<0.01), which indicated the eye drop could significantly keep basic tears secretory volume and tear film stability. And the expression of AR of group C was much higher than that of group B,which showed that available composition of the eye drops maybe display androgen-like activity.CONCLUSION:The main components of extract of Buddleja officinalis is the flavonoids which could significantly inhibit happening of dry eye of rat after androgen level lowered. Its mechanism is like androgen's and it could display androgen-like activity to keep basic tears secretory volume and tear film stability.