RESUMO
Prostate cancer is the most common cancer in men, with an incidence that is expected to increase in the coming years. Prostate cancer is usually diagnosed in men >65 years of age, thus the concurrent presence of cardiovascular diseases might influence the treatment, owing to the increased risk of cardiovascular mortality. The introduction of new drugs, such as abiraterone and enzalutamide for the management of metastatic disease has created further interest in treatment-related cardiovascular toxicities, although limited data from trials specifically designed to identify cardiovascular toxicities of these agents are currently available. The only available data are derived from published phase II-III study reports, expanded access or compassionate use programmes and meta-analyses of the effects of systemic therapies that are already approved for use in clinical practice or are in the early phases of development. These data are conflicting, although they seem to suggest that certain drugs are associated with an increased risk of cardiovascular adverse events. Clinical trial methodology could be improved by the enrolment of greater numbers of patients >65 years of age, and the use of comprehensive cardiological evaluations. Moreover, closer collaboration between oncologists and cardiologists is essential for the identification and/or management of cardiovascular adverse events in patients with prostate cancer.
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PURPOSE: Although radical cystectomy is still considered the standard of care for most localized muscle-invasive bladder cancer (MIBC) patients, bladder-sparing strategies with chemoradiotherapy have demonstrated comparable local control and survival rates when adjusting for tumor stage. We present a pooled analysis of individual patient data out of published trials with gemcitabine-based chemoradiotherapy for MIBC. METHODS AND MATERIALS: Individual patient data were collected from Institutions that enrolled patients into trials that evaluated gemcitabine-based chemoradiotherapy for MIBC. RESULTS: We identified eight studies published on gemcitabine-based radiochemotherapy and 190 patients were included in this analysis. A complete response (CR) was observed in 166 patients (93%). After a median follow up of 44.5months, 36 patients (18.9%) presented a bladder recurrence and 14 subsequently underwent cystectomy. The 5-year overall survival (OS), disease-specific survival (DSS), and cystectomy-free survival (CFS) rates were 59%, 80.9%, and 93.3%, respectively. The achievement of CR after chemoradiotherapy was the main prognostic variable which was associated with improved OS, DSS, and CFS. The treatment was well tolerated. CONCLUSION: This pooled analysis strengthens the evidence that chemoradiotherapy regimens with concurrent gemcitabine are feasible and well tolerated. Prospective randomized controlled trials are on-going to definitively assess the efficacy of gemcitabine-based chemoradiotherapy for MIBC.
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Antimetabólitos Antineoplásicos/uso terapêutico , Quimiorradioterapia , Desoxicitidina/análogos & derivados , Neoplasias da Bexiga Urinária/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/métodos , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Cistectomia , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatística como Assunto , Neoplasias da Bexiga Urinária/mortalidade , GencitabinaRESUMO
Over the last ten years, two new-generation hormonal drugs and two chemotherapeutic agents have been approved for the treatment of metastatic castration-resistant prostate cancer. Unfortunately, some patients have primary resistance to them and the others eventually develop secondary resistance. It has recently been suggested that the presence of androgen receptor splice variants plays a leading role in the primary and secondary resistance to the new hormonal drugs, whereas their presence seem to have only a partial effect on the activity of the chemotherapeutic agents. The aim of this paper is to review the published data concerning the role of androgen receptor splice variants in prostate cancer biology, and their potential use as biomarkers when making therapeutic decisions.
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The availability of new drugs capable of improving the overall survival of patients with metastatic castration-resistant prostate cancer has led to the possibility of using them sequentially in the hope of obtaining a cumulative survival benefit. The new agents have already been administered as third-line treatments in patients who have previously received them as second line in everyday clinical practice, but the efficacy of this practice is not yet supported by clinical trial data, and evidence of possible cross-resistance has reinforced the debate concerning the best sequence to use in order to maximise the benefit. Furthermore, the situation is further complicated by the possibility of administering new hormonal agents to chemotherapy-naïve patients, and novel chemotherapeutic agents to hormone-sensitive patients. This article critically reviews the available data concerning the sequential use of new drugs, and discusses the real evidence concerning their optimal positioning in the therapeutic strategy of metastatic castration-resistant prostate cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desenho de Fármacos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Animais , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/patologia , Taxa de SobrevidaRESUMO
AIM: High rate of non-target lesions in metastatic castration-resistant prostate cancer usually limits applicability of Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and this has led to a growing interest in using PET/computed tomography (CT). We prospectively investigated the role of (18)F-choline (FCH)-PET/CT in patients receiving enzalutamide after docetaxel. PATIENTS & METHODS: 30 patients were monitored by means of FCH-PET/CT before and during the treatment. A Cox proportional hazards regression model was used to assess the associations between metabolic parameters and clinical outcomes. RESULTS: Univariate analysis showed no significant correlation between biochemical and FCH-PET responses. Multivariate analysis showed that only baseline maximum standardized uptake value (SUVmax) significantly correlated with biochemical progression-free survival, radiological progression-free survival and overall survival. CONCLUSION: Our findings suggest that FCH-PET/CT may play a role in defining prognosis of patients receiving enzalutamide because baseline SUVmax proved to be an independent prognostic factor.
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Antineoplásicos/uso terapêutico , Neoplasias Ósseas/diagnóstico por imagem , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Colina/análogos & derivados , Colina/farmacocinética , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nitrilas , Feniltioidantoína/uso terapêutico , Tomografia por Emissão de Pósitrons , Modelos de Riscos Proporcionais , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual , Resultado do TratamentoRESUMO
AIM: To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer. PATIENTS & METHODS: The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes. RESULTS: We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3-4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival. CONCLUSION: The findings of this study suggest that toxicity is acceptable, survival is independent of patient's age and survival can be significantly prolonged by the use of new agents.
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Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel , Humanos , Masculino , Modelos de Riscos Proporcionais , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Retratamento , Estudos Retrospectivos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
UNLABELLED: Metastatic castration-resistant prostate cancer mainly affects older men, opening issues about the efficacy and safety of therapies in this population. We have demonstrated that abiraterone, a selective androgen biosynthesis inhibitor, is a safe and active therapeutic option in a subgroup of 47 very elderly adults (aged > 80 years) enrolled in the Italian named patient program, with a tolerability profile and clinical outcomes comparable to those of younger population. BACKGROUND: Prostate cancer mainly affects elderly men, who are often frail and whose reduced physiological reserves and multiple comorbidities increase the risk of side effects. The availability of new drugs has improved the overall survival (OS) of patients with castration-resistant prostate cancer (CRPC) but has increased the number of very elderly CRPC patients receiving anticancer drugs, raising questions about their efficacy and safety in this population. PATIENTS AND METHODS: We assessed the tolerability of abiraterone (AA) in a cohort of very elderly adults with metastatic CRPC (mCRPC) enrolled in the Italian AA named patient program and analyzed their clinical outcomes. We retrospectively reviewed the clinical records of 47 mCRPC patients aged > 80 years who had received AA after docetaxel. The Kaplan-Meier method was used to calculate OS and progression-free survival (PFS). Safety and clinical outcomes were also analyzed by age group (< 80 and > 80 years). Cox regression analysis was used to calculate the differences in PFS and OS between the groups according to the stratification variables. RESULTS: In very elderly men, the prostate-specific antigen response rate was 48.9%, and the median PFS and OS were 8 and 18 months, respectively. The differences in toxicities between the older and younger age groups were not major. The limitation of the present study was mainly its retrospective nature. CONCLUSION: Our data show that AA is active and safe in very elderly patients and leads to outcomes similar to those observed in younger patients, thus confirming that AA is a manageable therapeutic option for this patient population.
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Acetato de Abiraterona/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Ensaios de Uso Compassivo , Intervalo Livre de Doença , Docetaxel , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Neoplasias de Próstata Resistentes à Castração/mortalidade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Two new hormonal agents (NHAs), abiraterone and enzalutamide, and one chemotherapeutic agent, cabazitaxel (CABA) improved overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) who progress after docetaxel. Although several analyses of patient cohorts receiving a sequence of two different new agents (NAs) after docetaxel have been published, no definite conclusions can be drawn regarding the best treatment strategy. MATERIALS AND METHODS: All published studies reporting monthly OS rates of mCRPC patients receiving third-line NA after having previously received docetaxel and another NA have been analyzed. The treatments were merged into three groups: one NHA followed by another, one NHA followed by CABA, and CABA followed by one NHA. The cumulative monthly OS rates in each group were determined using a weighted-average approach. RESULTS: Thirteen retrospective studies including 1016 patients who received NHA/NHA (469), NHA/CABA (318) or CABA/NHA (229) were evaluated. The 12-month OS rates were 28.5%, 61.3%, and 76.4%, respectively. There were no statistically significant differences in terms of known prognostic factors. CONCLUSIONS: Although the retrospective nature of the studies and potential selection biases, our data seem to confirm the potential cumulative survival benefit of using the NAs sequentially after docetaxel. There was no clear superiority of any one of the three strategies, but a sequence that includes CABA seems to suggest a possible OS advantage.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Androstenos/administração & dosagem , Benzamidas , Progressão da Doença , Docetaxel , Humanos , Masculino , Nitrilas , Feniltioidantoína/administração & dosagem , Feniltioidantoína/análogos & derivados , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagemRESUMO
BACKGROUND: To assess the relationship between dosimetric parameters and the quality of life (QL) outcomes of patients with low-intermediate-risk localised prostate cancer (LPC) treated with low-dose-rate brachytherapy (LDR-BT). MATERIALS AND METHODS: We evaluated the participants in two consecutive prospective studies of the QL of patients treated with LDR-BT for LPC. QL was evaluated by means of a patient-completed questionnaire assessing non functional [physical (PHY) and psychological (PSY) well-being, physical autonomy (POW), social relationships (REL)] and functional scales [urinary (URI), rectal (REC), and sexual (SEX) function]; a scale for erectile function (ERE) was included in the second study. Urethra (D10 ≤ 210 Gy) and rectal wall constraints (V100 ≤ 0.5 cc) were used for pre-planning dosimetry and were assessed with post planning computerized tomography one month later for each patient. RESULTS: QL was assessed in 251 LPC patients. Dosimetry did not influence the non-functional scales. As expected, a progressive impairment in sexual and erectile function was reported one month after LDR-BT, and became statistically significant after the third year. Rectal function significantly worsened after LDR-BT, but the differences progressively decreased after the 1-year assessment. Overall urinary function significantly worsened immediately after LDR-BT and then gradually improved over the next three years. Better outcomes were reported for V100 rectal wall volumes of ≤ 0.5 cc and D10 urethra values of ≤ 210 Gy. CONCLUSIONS: The findings of this study show that dosimetric parameters influence only functional QL outcomes while non-functional outcomes are only marginally influenced.
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Adenocarcinoma/radioterapia , Braquiterapia/efeitos adversos , Neoplasias da Próstata/radioterapia , Qualidade de Vida , Dosagem Radioterapêutica , Atividades Cotidianas , Adenocarcinoma/psicologia , Idoso , Braquiterapia/métodos , Seguimentos , Genitália Masculina/efeitos da radiação , Humanos , Relações Interpessoais , Enteropatias/etiologia , Enteropatias/psicologia , Masculino , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Estudos Prospectivos , Neoplasias da Próstata/psicologia , Planejamento da Radioterapia Assistida por Computador , Reto/efeitos da radiação , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/psicologia , Inquéritos e Questionários , Uretra/efeitos da radiação , Bexiga Urinária/efeitos da radiação , Transtornos Urinários/etiologia , Transtornos Urinários/psicologiaRESUMO
BACKGROUND: The potential benefits of the introduction of electronic and mobile health (mHealth) information technologies, to support the safe delivery of intravenous chemotherapy or oral anticancer therapies, could be exponential in the context of a highly integrated computerized system. OBJECTIVE: Here we describe a safe therapy mobile (STM) system for the safe delivery of intravenous chemotherapy, and a home monitoring system for monitoring and managing toxicity and improving adherence in patients receiving oral anticancer therapies at home. METHODS: The STM system is fully integrated with the electronic oncological patient record. After the prescription of chemotherapy, specific barcodes are automatically associated with the patient and each drug, and a bedside barcode reader checks the patient, nurse, infusion bag, and drug sequence in order to trace the entire administration process, which is then entered in the patient's record. The usability and acceptability of the system was investigated by means of a modified questionnaire administered to nurses. The home monitoring system consists of a mobile phone or tablet diary app, which allows patients to record their state of health, the medications taken, their side effects, and a Web dashboard that allows health professionals to check the patient data and monitor toxicity and treatment adherence. A built-in rule-based alarm module notifies health care professionals of critical conditions. Initially developed for chronic patients, the system has been subsequently customized in order to monitor home treatments with capecitabine or sunitinib in cancer patients (Onco-TreC). RESULTS: The STM system never failed to match the patient/nurse/drug sequence association correctly, and proved to be accurate and reliable in tracing and recording the entire administration process. The questionnaires revealed that the users were generally satisfied and had a positive perception of the system's usefulness and ease of use, and the quality of their working lives. The pilot studies with the home monitoring system with 43 chronic patients have shown that the approach is reliable and useful for clinicians and patients, but it is also necessary to pay attention to the expectations that mHealth solutions may raise in users. The Onco-TreC version has been successfully laboratory tested, and is now ready for validation. CONCLUSIONS: The STM and Onco-TreC systems are fully integrated with our complex and composite information system, which guarantees privacy, security, interoperability, and real-time communications between patients and health professionals. They need to be validated in order to confirm their positive contribution to the safer administration of anticancer drugs.
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Antineoplásicos/uso terapêutico , Asma/terapia , Diabetes Mellitus/terapia , Hipertensão/terapia , Neoplasias/tratamento farmacológico , Telemedicina/métodos , Atitude do Pessoal de Saúde , Telefone Celular , Humanos , Sistemas de Informação , Itália , Aplicativos Móveis , Enfermagem Oncológica , Segurança do Paciente , Satisfação do Paciente , Projetos Piloto , Sistemas Automatizados de Assistência Junto ao LeitoRESUMO
BACKGROUND: The prognosis of younger patients with prostate cancer is unclear, and the very few studies assessing those with metastatic castration-resistant prostate cancer (mCRPC) have mainly involved patients treated with older therapies. The aim of this observational study was to evaluate the clinical outcomes of a contemporary series of docetaxel-treated patients with mCRPC who were 60 years and younger. PATIENTS AND METHODS: We retrospectively identified 134 patients who were 60 years and younger who were treated with docetaxel in 25 Italian hospitals and recorded their predocetaxel history of prostate cancer, their characteristics at the start of chemotherapy, and their postdocetaxel treatment history and outcomes. RESULTS: Most of the 134 consecutive patients with mCRPC received the standard 3-week docetaxel schedule; median progression-free survival (PFS) was 7 months, and 90 patients underwent further therapies after progression. The median overall survival (OS) from the start of docetaxel treatment was 21 months, but OS was significantly prolonged by the postprogression treatments, particularly those based on the new agents such as cabazitaxel, abiraterone acetate, or enzalutamide. OS was significantly shorter in the patients with a shorter interval between the diagnosis of prostate cancer and the start of docetaxel treatment; those who received hormonal treatment for a shorter period; those with shorter prostate-specific antigen doubling times; and those with lower hemoglobin levels, a worse performance status, and higher lactate dehydrogenase levels before starting treatment with docetaxel. CONCLUSIONS: The findings of this first study of clinical outcomes in a contemporary series of younger patients with mCRPC showed that their survival is similar to that expected in unselected patients with mCRPC who were of any age.
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Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
AIMS: The intermittent administration of chemotherapy is a means of preserving patients' quality of life (QL). The aim of this study was to verify whether the intermittent administration of docetaxel (DOC) improves the patients' QL. PATIENTS & METHODS: All patients received DOC 70 mg/m(2) every 3 weeks for eight cycles. The patients were randomized to receive DOC continuously or with a fixed 3-month interval after the first four DOC courses. RESULTS: The study involved 148 patients. There was no difference in QL between the groups receiving intermittent or continuous treatment. Intermittence had no detrimental effects on disease control. CONCLUSION: Although feasible and not detrimental, our results showed that true intermittent chemotherapy in metastatic castration-resistant prostate cancer patients failed to improve the patients' QL.
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Antineoplásicos/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel , Esquema de Medicação , Humanos , Masculino , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/mortalidade , Qualidade de Vida , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
The availability of active new drugs for the treatment of advanced castration-resistant prostate cancer has significantly prolonged overall survival, thus changing the natural history of the disease and raising the likelihood of observing metastases in atypical sites. This review of the literature describes the frequency, clinical-pathological features and presenting symptoms of non-liver gastrointestinal metastases (GIm) from prostate cancer. Its purpose is to increase clinical awareness of the increasing incidence of such GIm, contributing to the early detection, accurate diagnosis and, when feasible, appropriate management.
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Neoplasias Gastrointestinais/secundário , Neoplasias da Próstata/patologia , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/terapia , Humanos , Incidência , Masculino , Avaliação de Resultados em Cuidados de Saúde , PrognósticoRESUMO
BACKGROUND: The availability of new agents (NAs) active in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel treatment (abiraterone acetate, cabazitaxel, and enzalutamide) has led to the possibility of using them sequentially to obtain a cumulative survival benefit. OBJECTIVE: To provide clinical outcome data relating to a large cohort of mCRPC patients who received a third-line NA after the failure of docetaxel and another NA. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed the clinical records of patients who had received at least two successive NAs after the failure of docetaxel. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The independent prognostic value of a series of pretreatment covariates on the primary outcome measure of overall survival was assessed using Cox regression analysis. RESULTS AND LIMITATIONS: We assessed 260 patients who received one third-line NA between January 2012 and December 2013, including 38 who received a further NA as fourth-line therapy. The median progression-free and overall survival from the start of third-line therapy was, respectively, 4 mo and 11 mo, with no significant differences between the NAs. Performance status, and haemoglobin and alkaline phosphatase levels were the only independent prognostic factors. The limitations of the study are mainly due its retrospective nature and the small number of patients treated with some of the sequences. CONCLUSIONS: We were unable to demonstrate a difference in the clinical outcomes of third-line NAs regardless of previous NA therapy. PATIENT SUMMARY: It is debated which sequence of treatments to adopt after docetaxel. Our data do not support the superiority of any of the three new agents in third-line treatment, regardless of the previously administered new agent.
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Acetato de Abiraterona/uso terapêutico , Antineoplásicos/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/uso terapêutico , Idoso , Benzamidas , Estudos de Coortes , Intervalo Livre de Doença , Docetaxel , Humanos , Itália , Masculino , Análise Multivariada , Nitrilas , Feniltioidantoína/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Falha de Tratamento , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the safety and efficacy of abiraterone acetate (AA) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated in a compassionate named patient programme (NPP). PATIENTS AND METHODS: We retrospectively reviewed the clinical records of patients with mCRPC treated with AA at the standard daily oral dose of 1000 mg plus prednisone 10 mg/day in 19 Italian hospitals. RESULTS: We assessed 265 patients with mCRPC treated with AA. The most frequent (>1%) grade 3-4 toxicities were anaemia (4.2%), fatigue (4.2%), and bone pain (1.5%). The median progression-free survival was 7 months; median overall survival was 17 months after starting AA, and 35 months after the first docetaxel administration. Our study reproduced the clinical outcomes reported in the AA pivotal trial, including those relating to special populations such as the elderly, patients with a poor performance status, symptomatic patients, and patients with visceral metastases. CONCLUSIONS: Our data show the safety and activity of AA when administered outside clinical trials, and confirm the findings of the post-docetaxel pivotal trial in the patients as a whole population and in special populations of specific interest.
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Androstenos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstenos/efeitos adversos , Antineoplásicos/uso terapêutico , Ensaios de Uso Compassivo , Docetaxel , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
AIM: To identify factors predicting primary resistance to new-generation hormonal agents (NHAs), abiraterone acetate and enzalutamide in patients with castration-resistant prostate cancer (CRPC). PATIENTS & METHODS: Our hospital has conducted two successive named patient NHA programs. A total of 57 patients with progressive CRPC previously treated with first-line docetaxel-based chemotherapy received standard NHA doses: abiraterone acetate 1000 mg once-daily combined with prednisone (5 mg twice daily) or enzalutamide 160 mg once-daily. Patients, who were assessed monthly to check their hematological parameters and prostate-specific antigen (PSA) levels, also underwent imaging investigations every 3-4 months. In total, 24 variables were assessed as potential predictors of primary NHA resistance. RESULTS: Univariate analysis indicated that baseline pain and lactate dehydrogenase levels, and PSA levels after 1 month's treatment were predictive of primary NHA resistance. Only the predictive value of PSA levels after 1 month of treatment was confirmed at multivariate analysis. This factor strongly predicted progression-free and overall survival. CONCLUSION: RESULTS suggest the use of a simple and rapid method of identifying patients with primary resistance to NHAs: patients not achieving a ≥ 50% reduction in PSA levels within the first treatment month should undergo intensive investigations to verify whether they have primary resistance to NHAs.
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Androstadienos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feniltioidantoína/análogos & derivados , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Acetato de Abiraterona , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Progressão da Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/uso terapêutico , Prognóstico , Neoplasias da Próstata/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND: Enzalutamide is active in advanced castration-resistant prostate cancer (CRPC) patients, in whom it has shown to be able to increase survival. We report the enzalutamide effect on primary prostate tumors, assessed by changes of metabolic tumor activity detected by (18)F-fluorocholine-positron emission tomography/computerized tomography ((18)F-FCH PET/CT). PATIENTS AND METHODS: We treated 31 patients with pretreated metastatic CRPC in an enzalutamide named-patient program. All patients were initially evaluated and then followed up by means of repeated (18)F-FCH PET/CT examinations. We identified most radiotracer-avid lesions, which were defined as specific regions of interest (ROIs): for each ROI we defined the maximum radiotracer standardized uptake value (SUVmax) and the threshold-based volume of interest (VOI) with a cutoff SUV value ≥ 2.5. In the 12 patients who did not receive a radical treatment for localized disease, the prostate was also considered an ROI. RESULTS: The baseline prostate median SUVmax of 7.25 showed reductions of 25% (P = .012) and 43% (P = .009) after 3 and 7 months of enzalutamide treatment, respectively. The baseline median prostate VOI of 12.73 cm(3) showed a reduction of 73% (P = .002) at 3 months and a reduction of 90% (P = .005) at 7 months. CONCLUSION: In addition to the metabolic changes of metastatic lesions observed with enzalutamide in CRPC patients, our data have shown significant volume reductions of the primary tumors according to (18)F-FCH PET/CT evaluation. These results could suggest the potential of enzalutamide therapy for localized prostate cancer.
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Antineoplásicos/uso terapêutico , Feniltioidantoína/análogos & derivados , Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Benzamidas , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/administração & dosagem , Feniltioidantoína/uso terapêutico , Tomografia por Emissão de Pósitrons , Próstata/diagnóstico por imagem , RadiografiaRESUMO
AIM: The Italian Retrospective Analysis of Sorafenib as First or Second Target Therapy study assessed the efficacy and safety of sorafenib in metastatic renal cell carcinoma patients treated in the community. PATIENTS & METHODS: Patients receiving first- or second-line single-agent sorafenib between January 2008 and December 2010 were eligible. Retrospective data collection started in 2012 and covers at least 1-year follow-up. The primary end point was overall survival (OS). RESULTS: Median OS was 17.2 months (95% CI: 15.5-19.6): 19.9 months (95% CI: 15.9-25.3) in patients treated with first-line sorafenib and 16.3 months (95% CI: 13.1-18.2) with second-line sorafenib. Overall median (95% CI) progression-free survival was 5.9 months (95% CI: 4.9-6.7): 6.6 (95% CI: 4.9-9.3) and 5.3 months (95% CI: 4.3-6.0) in first- and second-line patients, respectively. CONCLUSION: The efficacy and safety of sorafenib in routine community practice was generally good, especially in relation to OS in patients treated in the second line, where results were similar to those seen in recent prospective clinical trials.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Feminino , Seguimentos , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Sorafenibe , Resultado do TratamentoRESUMO
The Leucine Zipper Tumor Suppressor 1 (LZTS1) is a tumor suppressor gene, located at chromosome 8p22, which is frequently altered in human cancer. In normal tissue, its ubiquitous expression regulates cell mitosis by the stabilization of microtubule networks. LZTS1-deficient mouse embryonic fibroblasts have been shown to have an accelerated mitotic progression, and a higher resistance to taxanes, microtubule-stabilizing drugs. We investigate the role of Lzts1 in paclitaxel-resistance in breast cancer cells. Downregulation of Lzts1 expression significantly decreases sensitivity to paclitaxel in vitro. We further analyzed Lzts1 expression by immunohistochemistry in 270 primary breast cancer samples and 16 normal breast specimens. Lzts1 was significantly downregulated in breast cancer samples and its deregulation was associated with a higher incidence of tumor recurrence, and to a worse overall survival. Moreover, Lzts1-negative tumors were associated with unfavorable outcome after taxanes-based therapy. Thus our data suggest that Lzts1 deregulation is involved in breast cancer and its immunohistochemical evaluation may serve as a prognostic factor for breast cancer therapy.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Proteínas de Ligação a DNA/biossíntese , Paclitaxel/farmacologia , Proteínas Supressoras de Tumor/biossíntese , Animais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Feminino , Inativação Gênica , Humanos , Imuno-Histoquímica , Células MCF-7 , Camundongos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Prognóstico , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
PI3K/AKT/mTOR pathway alterations are frequent in patients with infiltrating breast cancer (IBC). Their clinical and pathological relevance has been insufficiently documented. We evaluated PI3KCA for mutations and the expression of PTEN, AKT, mTOR and p70S6K by immunohistochemistry in 246 IBC patients treated with hormone therapy (median follow-up, 97 months). A PI3KCA mutation was observed in 50 out of 229 informative cases (21.8 %), PTEN loss in 107 out of 210 (51 %), moderate/high level of expression of AKT in 133 out of 188 (71 %), moderate/high level of expression of mTOR in 173 out of 218 (79 %) and moderate/high level of expression of p70S6K in 111 out of 192 cases (58 %). PI3KCA mutation was associated with the absence of Her2/neu amplification/overexpression and a low level of MIB1/Ki-67 labelling. The expression of p70S6K was associated with a high level of mTOR immunoreactivity, and high PTEN expression was associated with high AKT expression level. Univariate analysis showed that PI3KCA mutation status was not associated with clinical outcome in the series as a whole or in the node-negative subgroup. However, in the node-positive subgroup, exon 9 PI3KCA mutation was associated with unfavourable overall survival (OS), although its impact on the final model in multivariate analysis seemed to be limited. Of the other markers, only high p70S6K expression was associated with a significantly prolonged OS. PI3KCA mutation status is of limited prognostic relevance in oestrogen receptor-positive breast cancer patients treated with hormone therapy.