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1.
Crit Rev Oncol Hematol ; 174: 103682, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35421529

RESUMO

In recent years the introduction of immunotherapy has importantly changed the treatment landscape of advanced urothelial carcinoma. Several immune checkpoint inhibitors are now the standard of care as maintenance treatment after disease control with platinum-based first-line chemotherapy (avelumab), in subsequent lines (pembrolizumab) or as upfront therapy in platinum-ineligible patients (atezolizumab or pembrolizumab). Moreover, personalized therapy based on tumor molecular features has been developed. Namely, the increasing knowledge of the pathogenesis and molecular pathways underlying cancer development and progression is leading the introduction of target therapies such as the recently approved fibroblastic growth factor receptor (FGFR) inhibitor erdafitinib or the anti-nectin 4 antibody drug-conjugated enfortumab vedotin. Consequently, clinicians face new challenges, such as the choice of the best therapeutic sequence for each patient. The aim of this review is focusing on the emerging treatment options in metastatic urothelial carcinoma and discussing clinical features for choosing therapeutic sequencing.

2.
J Clin Pathol ; 75(1): 39-44, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33144356

RESUMO

AIMS: According to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abnormalities of the murine double minute 2 (MDM2) gene, but a few studies have been investigated them. We profiled MDM2 gene amplification in a series of urothelial carcinomas (UC) considering the molecular subtypes and expression of programmed death ligand 1 (PD-L1). METHODS: 117 patients with muscle-invasive UC (pT2-3) without (N0) or with (N+) lymph-node metastases were revised. Only cases with availability of in toto specimens and follow-up were studied. Tissue microarray was built. p53, ER, RB1, GATA-3, CK20, CK5/6, CD44 and PD-L1 (clone sp263) immunoexpression was evaluated. Fluorescent in situ hybridisation was assessed by using the HER-2/neu, FGFR-3, CDKN2A and MDM2 probes. True (ratio 12q/CEP12 >2) MDM2 gene amplification was distinguished from polyploidy/gains (ratio <2, absolute copy number of MDM-2 >2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotypes. Statistical analysis was performed. RESULTS: 6/50 (12%) cases (5 N0 and 1 N+) were amplified for MDM2 without matching to molecular phenotypes. Of 50, 14 (37%) cases expressed PD-L1 at 1% cut-off; 3/50 (9%) at >50% cut-off; of these, 2 cases on side of neoplasia among inflammatory cells. Only one out of six (17%) cases amplified for MDM2 showed expression (>50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC. CONCLUSION: MDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo/single targeted therapies.


Assuntos
Antígeno B7-H1/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Biomarcadores/metabolismo , Feminino , Amplificação de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Fenótipo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Análise Serial de Tecidos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
3.
Eur J Cancer ; 155: 127-135, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371442

RESUMO

BACKGROUND: This study was designed to demonstrate the non-inferiority (NI) in overall survival (OS) of suspension of androgen deprivation therapy (ADT) versus maintenance and intermittent versus continuous docetaxel administration in metastatic castration-resistant prostate cancer (mCRPC) patients. PATIENTS AND METHODS: mCRPC patients were randomised to first-line docetaxel with maintenance or suspension of ADT. Patients attaining a prostate-specific antigen (PSA) response after four chemotherapy cycles underwent second randomisation to receive continuous or intermittent docetaxel therapy. Six hundred patients were to be randomised to achieve 80% statistical power to demonstrate an NI hazard ratio (HR) of 1.25 of interruption versus maintenance of ADT. RESULTS: The trial was prematurely closed when 198 participants were randomised. OS was similar in patients who continued (N = 96) versus those who interrupted (n = 102) ADT during docetaxel therapy (HR 0.98, 95% confidence interval [CI] 0.72-1.33] and those on a continuous (N = 35) versus an intermittent (N = 42) docetaxel schedule (HR 0.86, 95% CI 0.55-1.43). No difference in radiological progression-free survival, PSA response, or toxicity was observed between the study arms. The actual NI hazard margins of OS in Arms A and B patients were 1.33 and 1.43, respectively. CONCLUSIONS: This trial enrolled one-third of the planned patients; this main weakness dramatically limits the interpretation of the results. ADT discontinuation and switching to an intermittent schedule did not seem to affect docetaxel efficacy. The absence of testosterone recovery in the majority of patients could have been a contributory factor. In men with mCRPC, ADT discontinuation should only be done with regular biochemical and clinical monitoring, with the option of quickly restarting ADT at disease progression.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Antagonistas de Androgênios/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Docetaxel/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Análise de Sobrevida
4.
Eur J Cancer ; 155: 56-63, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34358777

RESUMO

BACKGROUND: Pre-clinical data suggest that docetaxel and enzalutamide interfere with androgen receptor translocation and signalling. The aim of this study is to assess the efficacy of their concurrent administration in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). METHODS: In this open-label, randomised, phase II trial, previously untreated mCRPC patients were randomised 1:1 to receive eight 21-d courses of docetaxel 75 mg/m2, oral prednisone 5 mg twice daily and oral enzalutamide 160 mg/d (arm DE), or the same treatment without enzalutamide (arm D). The primary end-point was the percentage of patients without investigator-assessed disease progression 6 months after the first docetaxel administration. RESULTS: The 246 eligible patients were randomly assigned to receive docetaxel, prednisone and enzalutamide (n = 120) or docetaxel and prednisone (n = 126). The 6-month progression rate was 12.5% (95% confidence interval [CI] 8.1-20.6) in arm DE and 27.8% (95% CI 22.8-39.4) in arm D (chi-squared test 10.01; P = 0.002). The most frequent grade III-IV adverse events were fatigue (12.5% in arm DE versus 5.6% in arm D), febrile neutropenia (9.3% versus 4.0%) and neutropenia (7.6% versus 5.6%). CONCLUSIONS: The combination of enzalutamide and docetaxel appears to be more clinically beneficial than docetaxel alone in previously untreated mCRPC patients, although serious adverse events were more frequent. Our findings suggest that first-line treatment with this combination could lead to an additional clinical benefit when prompt and prolonged disease control is simultaneously required. Clearly, these results should be considered cautiously because of the study's phase II design and the absence of an overall survival benefit. TRIAL REGISTRATION NUMBERS: EudraCT 2014-000175-43 - NCT02453009.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/uso terapêutico , Docetaxel/uso terapêutico , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Prednisona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Docetaxel/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/farmacologia
5.
Eur J Cancer ; 132: 17-23, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32311643

RESUMO

The novel severe acute respiratory syndrome coronavirus-2 pandemic is a global health problem, which started to affect China by the end of 2019. In Europe, Italy has faced this novel disease entity (named novel coronavirus disease [COVID-19]) first and severely. COVID-19 represents a significant hurdle for public health services and a potential harm for patients with cancer. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. In the midst of the epidemic in Italy, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of oncologists and the implementation of containment measures of COVID-19 diffusion. Overall, 122 head physicians participated in this survey, with a homogeneous distribution on the national territory. Results show that the following measures for oncologic patients have been promptly implemented through the whole country: use of protective devices, triage of patients accessing the hospital, delay of non-urgent visits and use of telemedicine. Results of this survey suggest that Italian oncology departments have promptly set a proactive approach to the actual emergency. Oncologists need to preserve the continuum of care of patients, as the benefit of ensuring a well-delivered anti-cancer treatment plan outweighs the risk of COVID-19 infection. International cooperation is an important starting point, as heavily affected nations can serve as an example to find out ways to safely preserve health activity during the pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Oncologia/organização & administração , Neoplasias , Pneumonia Viral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Humanos , Itália/epidemiologia , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
6.
Liver Int ; 40(3): 704-711, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31773848

RESUMO

BACKGROUND: An accurate risk-stratification is key to optimize the benefit-to-risk ratio of palliative treatment in advanced biliary cancer. We aimed at assessing the impact of the prognostic nutritional index (PNI) on survival and treatment response in advanced biliary cancer (ABC) receiving first-line chemotherapy. METHODS: Medical records of ABC treated with standard chemotherapy at the Modena Cancer Centre were retrospectively reviewed for variables deemed of potential interest, including the PNI. Univariate and multivariate analyses were performed to investigate the association between the covariates and overall survival (OS). RESULTS: 114 ABC fulfilled the inclusion criteria and made up the training cohort. A PNI cut-off value of 36.7 was established using the receiver operating characteristic (ROC) analysis. At both the univariate and the multivariate analysis, low PNI value (<36.7) was associated with shorter OS (P = .0011), together with increased NLR (P = .0046) and ECOG >1 (P < .0001). The median OS was 5.4 vs 12.1 months in the low- vs high PNI-group. Moreover, a PNI value >36.7 resulted in a higher disease control in patients treated with gemcitabine/platinum combination (61.4% vs 34.3%). These results were validated in an independent cohort of 253 ABC. CONCLUSIONS: We demonstrated and externally validated a prognostic role for the PNI in ABC treated with first-line chemotherapy. Although the PNI turned out to be predictive in the subset of patients receiving platinum/gemcitabine combination, future prospective confirmation is needed.


Assuntos
Neoplasias , Avaliação Nutricional , Humanos , Prognóstico , Curva ROC , Estudos Retrospectivos
7.
Eur Urol Oncol ; 2(6): 699-707, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31542243

RESUMO

BACKGROUND: In selected metastatic renal cell carcinoma (mRCC) patients, radical metastasectomy followed by observation is a potential strategy. It is still to be defined whether systemic therapy should be administered following metastasectomy. OBJECTIVE: To assess the potential benefit of postoperative treatment with sorafenib compared with observation alone after radical metastasectomy in mRCC patients. DESIGN, SETTING, AND PARTICIPANTS: The RESORT trial was a multicenter, randomized, open-label, phase 2 study conducted between November 2012 and November 2017 in Italy. Patients with clear-cell mRCC pretreated with nephrectomy and undergoing radical metastasectomy (three or fewer lesions) were eligible for the study. Patients were randomized (1:1) within 12 wk from metastasectomy to sorafenib (standard dose 400 mg twice daily) or observation for a maximum of 52 wk. Stratification factors were interval from nephrectomy, site, and number of lesions. Overall, 76 patients were screened and 69 were randomized: 33 were assigned to sorafenib and 36 to observation. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints were overall survival and the safety profile. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RFS curves were estimated with the Kaplan-Meier method, and the log-rank test was used to statistically compare the curves. RESULTS AND LIMITATIONS: At a median follow-up of 38 mo, median RFS was 37 mo (95% confidence interval [CI] 20-not available [NA]) in the observation arm versus 21 mo (95% CI 11-NA) in the sorafenib arm (log-rank test p = 0.404), with 12-, 24-, and 36-mo RFS probability of 74% versus 63%, 59% versus 49%, and 50% versus 41%, respectively, in the observation versus the sorafenib arm. Any-grade adverse event (AE) rates were 84% in the sorafenib arm and 31% in the observation arm; grade ≥3 AE rates were 22% and 3% in the sorafenib and the observation arm, respectively, with a rate of treatment discontinuation for AEs of 19% in the sorafenib arm. CONCLUSIONS: This prospective study showed that systemic treatment with sorafenib did not increase RFS as compared with observation in mRCC patients following radical metastasectomy. PATIENT SUMMARY: This article reports the clinical outcome of patients with metastatic renal cell carcinoma treated with sorafenib or managed with an observation-alone strategy after the radical surgery of metastases. We found that sorafenib did not improve the patient outcome in terms of relapse-free survival in this selected population.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/cirurgia , Metastasectomia/métodos , Sorafenibe/uso terapêutico , Adulto , Idoso , Antineoplásicos/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sorafenibe/farmacologia
8.
Tumori ; 105(4_suppl): 3-12, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31264522

RESUMO

In the past two decades, the treatment landscape for patients with metastatic renal cell carcinoma has significantly changed thanks to the approval of several targeted molecular therapies (VEGF and mTOR inhibitors) and recently immune-checkpoint inhibitors. The Italian Association of Medical Oncology (AIOM) Renal Cell Cancer (RCC) Guidelines Panel has developed clinical guidelines to provide evidence-based information and recommendations to oncologists, urologists and all professionals involved in the management of patients with renal cell cancer.


Assuntos
Neoplasias Renais/tratamento farmacológico , Oncologia/normas , Carcinoma/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Itália
9.
Clin Cancer Res ; 25(13): 3839-3846, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30967420

RESUMO

PURPOSE: Inflammation indexes and body mass index (BMI) are easily evaluated, predict survival, and are potentially modifiable. We evaluated the potential association of inflammatory indexes and BMI with the clinical outcome of patients with renal cell carcinoma (RCC) undergoing immune checkpoint inhibitor therapy. EXPERIMENTAL DESIGN: A prospective cohort of patients with metastatic RCC treated with nivolumab enrolled in the Italian Expanded Access Program from July 2015 through April 2016 was examined. Reference measures of inflammation were identified for neutrophil-to-lymphocyte ratio (NLR)

Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Inflamação/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores , Índice de Massa Corporal , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Inflamação/diagnóstico , Estimativa de Kaplan-Meier , Neoplasias Renais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Prognóstico , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Cancers (Basel) ; 12(1)2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31905816

RESUMO

Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51-10.88) and 11.57 months (95% CI 10.90-not reached (NR)) as second-line and 11.38 months (95% CI 5.79-NR) and NR (95% CI 11.51-NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib-nivolumab and 25.64 months and NR with nivolumab-cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39; 95% CI 1.24-4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04-2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33; 95%CI, 1.16-4.69, p = 0.018) and Hb levels (HR = 3.12; 95%CI 1.18-8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72; 95%CI 1.04-7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.

11.
Clin Genitourin Cancer ; 16(4): e945-e951, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29753637

RESUMO

BACKGROUND: The randomized phase 3 METEOR study confirmed a survival benefit of cabozantinib over everolimus in patients with metastatic renal-cell carcinoma (mRCC) with disease that progressed after treatment with at least one previous antiangiogenic inhibitor. The aim of this analysis was to evaluate the safety and activity of cabozantinib in an unselected population. METHODS: Data were collected across 24 Italian centers. Cabozantinib therapy was initiated at physician request between September and December 2016. Patients with mRCC with disease that progressed after one or more prior systemic treatment were evaluated. Cabozantinib 60 mg was administered orally once daily. Doses were reduced to 40 mg or 20 mg in patients experiencing grade 3 or intolerable grade 2 adverse events (AEs). RESULTS: Data from 96 patients were evaluated. Cabozantinib was administered as second-line therapy in 28 patients (29%) and as third-line therapy in 18 patients (19%), while the remaining 50 patients (52%) received cabozantinib in further treatment lines. Sixty-six patients began therapy with the full dose of 60 mg. Because of poor performance status, 29 patients began therapy with a reduced dose of 40 mg and 1 patient with 20 mg. At the time of our analysis, grade 3/4 AEs were observed in 35 patients (36%). Only 5 patients discontinued treatment as a result of AEs. Partial response was observed in 35 patients (36%), whereas 33 (34%) had stable disease and 28 (30%) progressive disease. Median progression-free survival was 8.0 months. CONCLUSION: Cabozantinib showed acceptable tolerability and activity in a large unselected population treated according to everyday clinical practice.


Assuntos
Anilidas/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Piridinas/administração & dosagem , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anilidas/efeitos adversos , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Piridinas/efeitos adversos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
12.
Future Oncol ; 14(5): 443-448, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29318908

RESUMO

AIM: The aim of this study is to evaluate cardiotoxicity of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer patients (pts) with cardiovascular comorbidities or coronary artery disease (CAD) risk factors. PATIENTS & METHODS: We prospectively analyzed pts receiving AA in order to evaluate correlations between cardiotoxicity onset and CAD risk factors or cardiovascular comorbidities. RESULTS: Eighty-seven pts were enrolled, with median treatment duration of 9 months (1-44). At baseline, 84 pts (96%) had CAD risk factors. During treatment four pts (4; 6%) developed hypertension and 26 pts (30%) worsened the preexisting hypertension. Median left ventricular ejection fraction were 64 and 63% at baseline and after treatment, respectively. CONCLUSION: AA appears to be safe in pts with cardiovascular comorbidities or CAD risk factors.


Assuntos
Acetato de Abiraterona/efeitos adversos , Acetato de Abiraterona/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Acetato de Abiraterona/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Cardiotoxicidade , Doenças Cardiovasculares , Comorbidade , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/complicações , Fatores de Risco
13.
Pathol Oncol Res ; 24(3): 447-456, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28695322

RESUMO

The new WHO 2016 classification of renal neoplasia encounters the new entity called "clear cell papillary renal cell carcinoma" (ccpRCC). The ccpRCC has been long included as a subtype of clear cell RCC histotype and it actually ranges from 2 to 9% in different routinely available cohort of renal carcinomas. Of important note, ccpRCC does not show any recurrences or metastases or lymph-node invasion and the outcome is always good. We reviewed twenty-four publications with available follow-up for patients (no. 362) affected by clear cell papillary RCCs/renal adenomatoid tumours and notably ccpRCC harbors an indolent clinical behavior after a mean of 38 months (3,5 years) of follow-up. This paper reviews the histological, molecular and clinical features characterizing ccpRCC, with the goal of focusing the knowledge of the benign fashion of this new tumour entity, supporting the idea of a new renal cell adenoma recruited morphologically from ex conventional clear cell RCC tumours.


Assuntos
Adenoma/patologia , Carcinoma Papilar/patologia , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/patologia , Neoplasias Renais/classificação , Neoplasias Renais/patologia , Estadiamento de Neoplasias/normas , Humanos
14.
Oncology ; 92(5): 269-275, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28208153

RESUMO

PURPOSE: Pancreatic metastases (PM) from renal cell carcinoma (RCC) have been associated with long-term survival. The aim of this study was to evaluate the outcome of RCC patients with multiple glandular metastases (MGM) treated with targeted therapies (TTs). METHODS: Sixty-four MGM patients treated between 1993 and 2014 were retrospectively identified from a database of 274 RCC patients with PM from 11 European centers. The survival of MGM patients was compared with that of both patients with PM only and a cohort of 325 RCC patients with non-GM (control group) treated with TTs. Survival was estimated using the Kaplan-Meier method and was statistically compared using the log-rank test. RESULTS: Fifty-six patients (88%) had at least 2 MGM, 7 patients (11%) had 3 MGM and 1 patient had 4 MGM, while non-GM were present in the remaining patients. The median overall survival (OS) was 54.2 months for MGM and 73.4 months for patients with PM only. The median OS in the control group was 22.7 months and statistically inferior to both MGM (p < 0.001) and PM patients (p < 0.001). CONCLUSION: MGM from RCC are associated with a remarkable survival. Despite some limitations, these findings suggest that GM might be considered a predictor of a favorable prognosis.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Terapia de Alvo Molecular , Neoplasia Endócrina Múltipla/tratamento farmacológico , Adulto , Idoso , Carcinoma de Células Renais/patologia , Europa (Continente) , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla/secundário , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
15.
Front Pharmacol ; 7: 123, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27242530

RESUMO

BACKGROUND: Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting. PATIENTS AND METHODS: We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics. RESULTS: We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6-6.5) and the median OS was 17.1 months (8.8-25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days. CONCLUSION: A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS.

17.
PLoS One ; 11(4): e0151662, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27064898

RESUMO

Pancreatic metastases from renal cell carcinoma are uncommon and their prognostic significance is not well defined. In this analysis we evaluated the outcome of patients with pancreatic metastases treated with either targeted therapies or local treatment to the pancreas. Patients with pancreatic metastases from renal cell carcinoma treated between 1993 and 2014 were identified from 11 European centers. Clinical records were retrospectively reviewed. Kaplan-Meier method and log-rank test were used to evaluate progression-free survival and overall survival. Cox's proportional hazard models were used for survival analysis. In total, 276 PM patients were evaluated, including 77 (28%) patients treated by either surgery or radiotherapy to the pancreas, and 256 (93%) who received systemic therapy. Median time from nephrectomy to diagnosis of pancreatic metastases was 91 months (IQR 54-142). Disease control rate after first-line TTs was 84%, with a median progression-free survival of 12 months (95% CI 10-14). Median overall survival was 73 months (95% CI 61-86) with a 5-year OS of 58%. Median OS of patients treated with local treatment was 106 months (95% CI 78-204) with a 5-year overall survival of 75%. On multivariable analysis, nephrectomy (HR 5.31; 95%CI 2.36-11.92; p<0.0001), Memorial Sloan Kettering/International Metastatic RCC Database Consortium prognostic score (HR 1.45, 95% CI 0.94-2.23 for intermediate vs good vs risk; HR 2.76 95%, CI 1.43-5.35 for poor vs good risk p = 0.0099) and pancreatic local treatment (HR 0.48; 95%CI 0.30-0.78 p = 0.0029) were associated with overall survival. Difference in median OS between patients with PM and that reported in a matched-control group of mRCC patients with extrapancreatic metastases was statistically significant (p < .0001). Pancreatic metastases from renal cell carcinoma usually occur years after nephrectomy, are associated with an indolent behavior and a prolonged survival. Targeted therapies and locoregional approaches are active and achieve high disease control rate.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Terapia de Alvo Molecular/mortalidade , Nefrectomia/mortalidade , Neoplasias Pancreáticas/secundário , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/terapia , Terapia Combinada , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
18.
Future Oncol ; 12(4): 493-502, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26776493

RESUMO

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.


Assuntos
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 Tratamento
19.
Panminerva Med ; 58(2): 121-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26785374

RESUMO

BACKGROUND: The aim of this paper was to report definitive outcome of prostate cancer patients treated with dose escalation during a period of 12.5 years. METHODS: From October 1999 to March 2012 we treated 1080 patients affected by prostate cancer, using External Beam Radiotherapy (EBRT). The mean age was 69.2 years. Most of the patients (69%) were staged as cT2, Gleason Score (GS)<7; the mean iPSA 18 ng/mL; the rate of clinical positive nodes was 1%. Our intention to treat was the following: for low risk patients 72 Gy; for intermediate risk patients 75.6 Gy and for high-very high risk patients 79.2 Gy in 1.8 Gy/day fractions. From 2008 we changed the fractionation scheme and the doses were the following: for low risk patients 74 Gy and for intermediate and high-very high risk patients 78 Gy in 2.0 Gy/day fractions. Whole pelvis irradiation was performed in high-very high risk patients with 43.2-50.4 Gy in 1.8 Gy per day. The mean follow-up was 81 months. RESULTS: For the whole population at 5 and 10 years, the prostate cancer specific overall survival (CSOS) was 96.7% and 92.2% respectively; the clinical disease free survival (CDFS) 88% and 77%; the biochemical disease free survival (BDFS) 75% and 58.5%. The 5 and 10 years CSOS was 98% and 96% respectively for low risk, 96% and 92% for intermediate risk and 89% and 82% for high-very high risk patients. In intermediate and high-very high risk groups at 5 and 10 years the CSOS was 95.2% and 89.2% respectively, the CDFS 84.5% and 70% and the BDFS 70% and 51% respectively. In high-very high risk patients at 5 and 10 years the CSOS were respectively 89% and 82% the CDFS was 78% and 61% and BDFS was 61% and 34%. In whole patient population the BDFS was related with the dose level (P=0.006) as well as the CDFS (P=0.003) with a cut off of 75.6 Gy. In the subgroup of intermediate plus high-very high risk patients the BDFS and the CDFS were dose-related with a cut off of 75.6 Gy (P=0.007 and P=0.0018 respectively). Finally, in the subgroup of high-very high risk patients we found that the CSOS, the BDFS and the CDFS were related to the dose level with a cut-off of 77.7 Gy (P=0.017; P=0.006 and P=0.038, respectively). Overall gastrointestinal (GI) acute and late G2 toxicities were respectively 5 % and 3.8%; GI acute and late >G3 toxicities were respectively 0.5% and 0.9%; acute and late >G2 genitourinary (GU) toxicities were respectively 10.5% and 2.6%; finally GU acute and late >G3 toxicities were respectively 0.6% and 0.5%. CONCLUSIONS: The dose escalation is not relevant for the outcome in low risk patients that can benefit from relatively moderate doses (72-74 Gy). For intermediate and high-very high risk patients the dose becomes significant to levels above 75.6 Gy; particularly in high-very high risk doses >77.7 Gy correlate with an improved outcome. Patients receiving dose >77.7 Gy presented a higher rate of overall GI and GU toxicity, but the number of grade >2 remains low. Our results, consolidated by a long follow-up, corroborate the literature data, confirming that 3D-CRT can allow a safe dose escalation without significantly increasing the severe toxicity.


Assuntos
Neoplasias da Próstata/radioterapia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Relação Dose-Resposta à Radiação , Seguimentos , Trato Gastrointestinal/efeitos da radiação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Sistema Urogenital/efeitos da radiação
20.
Sci Rep ; 5: 18670, 2015 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-26690845

RESUMO

We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.


Assuntos
Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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