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The standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is now a combination of androgen deprivation therapy plus an androgen receptor-targeted therapy (abiraterone, apalutamide, enzalutamide or darolutamide), with or without chemotherapy (docetaxel). The selection of suitable patients for each therapeutic approach has become a determining factor to ensure efficacy and minimize side effects. This article combines recent clinical evidence with the accumulated experience of experts in medical oncology, radiation oncology and urology, to provide a comprehensive view and therapeutic recommendations for mHSPC.
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In castration-resistant prostate cancer (CRPC) patients, observational studies have reported that statins may boost the antitumor activity of abiraterone (AA) and data suggest an improvement in efficacy; conclusions with vitamin D are less clear but an eventual benefit has been pointed. We conducted a post hoc analysis of individual patient data of CRPC patients treated with prednisone and/or AA with or without statins/vitamin D on randomized clinical trials. In the COU-AA-301 trial, use of AA with statin and vitamin D reduced the risk of death by 38% (p = 0.0007) while AA alone was associated with a decrease of 10% (p = 0.025), compared to prednisone alone. Meanwhile, in the COU-AA-302 trial, use of AA plus statin plus vitamin D was associated with a reduced risk of death of 26% (p = 0.0054). In this data analysis from two prospective randomized clinical trials, statin and vitamin D use was associated with superior overall survival in metastatic CRPC patients treated with AA and prednisone. To our knowledge, this is the first report suggesting the impact of statin plus vitamin D in this population. New strategies using big data may help to clarify these questions easily and in a most cost-effective approach.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Vitamina D/administración & dosificación , Androstenos/uso terapéutico , Quimioterapia Combinada , Humanos , Masculino , Metástasis de la Neoplasia , Prednisona/uso terapéutico , Estudios Prospectivos , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background and purpose. In glioblastoma, tumor progression appears to be triggered by expression of VEGF, a regulator of blood vessel permeability. Bevacizumab is a monoclonal antibody that inhibits angiogenesis by clearing circulating VEGF, resulting in a decline in the contrast-enhancing tumor, which does not always correlate with treatment response. Our objectives were: (1) to evaluate whether changes in DSC perfusion MRI-derived leakage could predict survival in recurrent glioblastoma, and (2) to estimate whether leakage at baseline was related to treatment outcome. Materials and methods. We retrospectively analyzed DSC perfusion MRI in 24 recurrent glioblastomas treated with bevacizumab as second line chemotherapy. Leakage at baseline and changes in maximum leakage between baseline and the first follow-up after treatment were selected for quantitative analysis. Survival univariate analysis was made constructing survival curves using Kaplan-Meier method and comparing subgroups by log rank probability test. Results. Leakage reduction at 8 weeks after initiation of bevacizumab treatment had a significant influence on overall survival (OS) and progression-free survival (PFS). Median OS and PFS were 2.4 and 2.8 months longer for patients with leakage reduction at the first follow-up. Higher leakage at baseline was associated with leakage reduction after treatment. Odds ratio of treatment response was 9 for patients with maximum leakage at baseline >5. Conclusions. Leakage decrease may predict OS and PFS in recurrent glioblastomas treated with bevacizumab. Leakage reduction postulates as a potential biomarker for treatment response evaluation. Leakage at baseline seems to predict response to treatment, but was not independently associated with survival (AU)
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Adulto , Humanos , Glioblastoma/complicaciones , Glioblastoma/tratamiento farmacológico , Bevacizumab/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/instrumentación , Espectroscopía de Resonancia Magnética/métodos , Anticuerpos Monoclonales/uso terapéutico , 28599 , Estimación de Kaplan-Meier , Oportunidad RelativaRESUMEN
BACKGROUND AND PURPOSE: In glioblastoma, tumor progression appears to be triggered by expression of VEGF, a regulator of blood vessel permeability. Bevacizumab is a monoclonal antibody that inhibits angiogenesis by clearing circulating VEGF, resulting in a decline in the contrast-enhancing tumor, which does not always correlate with treatment response. Our objectives were: (1) to evaluate whether changes in DSC perfusion MRI-derived leakage could predict survival in recurrent glioblastoma, and (2) to estimate whether leakage at baseline was related to treatment outcome. MATERIALS AND METHODS: We retrospectively analyzed DSC perfusion MRI in 24 recurrent glioblastomas treated with bevacizumab as second line chemotherapy. Leakage at baseline and changes in maximum leakage between baseline and the first follow-up after treatment were selected for quantitative analysis. Survival univariate analysis was made constructing survival curves using Kaplan-Meier method and comparing subgroups by log rank probability test. RESULTS: Leakage reduction at 8 weeks after initiation of bevacizumab treatment had a significant influence on overall survival (OS) and progression-free survival (PFS). Median OS and PFS were 2.4 and 2.8 months longer for patients with leakage reduction at the first follow-up. Higher leakage at baseline was associated with leakage reduction after treatment. Odds ratio of treatment response was 9 for patients with maximum leakage at baseline >5. CONCLUSIONS: Leakage decrease may predict OS and PFS in recurrent glioblastomas treated with bevacizumab. Leakage reduction postulates as a potential biomarker for treatment response evaluation. Leakage at baseline seems to predict response to treatment, but was not independently associated with survival.
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Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/mortalidad , Medios de Contraste , Glioblastoma/mortalidad , Imagen por Resonancia Magnética/métodos , Recurrencia Local de Neoplasia/mortalidad , Adulto , Anciano , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Femenino , Estudios de Seguimiento , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Perfusión , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Purpose: The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status. Methods/patients: Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact. Results: In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment. Conclusion: This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG (AU)
No disponible
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Humanos , Masculino , Femenino , Adulto Joven , Persona de Mediana Edad , Anciano , Glioma/diagnóstico , Glioma/tratamiento farmacológico , Antineoplásicos Alquilantes/uso terapéutico , Recurrencia Local de Neoplasia/complicaciones , Recurrencia Local de Neoplasia/tratamiento farmacológico , Disonancia Cognitiva , Dexametasona/uso terapéutico , Resultado del Tratamiento , Evaluación de Eficacia-Efectividad de Intervenciones , Estudios Retrospectivos , Calidad de Vida/psicología , Protocolos Clínicos , Estimación de Kaplan-MeierRESUMEN
PURPOSE: The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status. METHODS/PATIENTS: Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact. RESULTS: In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment. CONCLUSION: This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG.
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Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Compuestos de Nitrosourea/uso terapéutico , Compuestos Organofosforados/uso terapéutico , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Femenino , Glioma/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Metronomic administration of the same chemotherapy agents (lower doses with closer intervals) may optimize their antiangiogenic properties. The aim of our study was to determine the efficacy and safety of a metronomic regimen based in non-pegylated liposomal doxorubicin (NPLD) in advanced breast cancer patients. METHODS: Clinical records of patients with pretreated advanced breast cancer and who were treated with the Metronomic-Cooper-type regimen consisting of weekly fixed doses of NPLD (30 mg IV) plus 5-Fluorouracil (5-FU) (500 mg IV) plus vincristine (0.25 mg IV) and daily oral cyclophosphamide (50 mg) plus prednisone (20 mg) were reviewed. RESULTS: In 84 pretreated patients, a tumor response was observed in 38 patients (45 %); stable disease was observed in 23 patients (27 %). Median progression-free survival (PFS) time to progression was 8.4 months and median overall survival (OS) was 21 months. The most common grade 2-3 hematologic adverse event was neutropenia, which was observed in 47 patients (56 %). Febrile neutropenia was observed in 10 patients (12 %). The most common non-hematologic adverse events were asthenia and mucositis which were observed in 60 patients (71 %) and 26 patients (31 %), respectively. Three patients (4 %) experienced an asymptomatic decline of the left ventricular ejection fraction. CONCLUSIONS: NPLD-based metronomic regimen was effective and safe in pretreated advanced breast cancer patients. It could be considered as an appealing option to treat patients previously exposed to anthracyclines (AU)
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Humanos , Masculino , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/secundario , Administración Metronómica , Mucositis/diagnósticoRESUMEN
PURPOSE: Metronomic administration of the same chemotherapy agents (lower doses with closer intervals) may optimize their antiangiogenic properties. The aim of our study was to determine the efficacy and safety of a metronomic regimen based in non-pegylated liposomal doxorubicin (NPLD) in advanced breast cancer patients. METHODS: Clinical records of patients with pretreated advanced breast cancer and who were treated with the Metronomic-Cooper-type regimen consisting of weekly fixed doses of NPLD (30 mg IV) plus 5-Fluorouracil (5-FU) (500 mg IV) plus vincristine (0.25 mg IV) and daily oral cyclophosphamide (50 mg) plus prednisone (20 mg) were reviewed. RESULTS: In 84 pretreated patients, a tumor response was observed in 38 patients (45 %); stable disease was observed in 23 patients (27 %). Median progression-free survival (PFS) time to progression was 8.4 months and median overall survival (OS) was 21 months. The most common grade 2-3 hematologic adverse event was neutropenia, which was observed in 47 patients (56 %). Febrile neutropenia was observed in 10 patients (12 %). The most common non-hematologic adverse events were asthenia and mucositis which were observed in 60 patients (71 %) and 26 patients (31 %), respectively. Three patients (4 %) experienced an asymptomatic decline of the left ventricular ejection fraction. CONCLUSIONS: NPLD-based metronomic regimen was effective and safe in pretreated advanced breast cancer patients. It could be considered as an appealing option to treat patients previously exposed to anthracyclines.