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1.
Per Med ; 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34873959

RESUMO

Although immunotherapy has recently revolutionized standard of care in different cancer types, prostate cancer has generally failed to show dramatic responses to immune checkpoint inhibitors. As in other tumors, the goal in prostate cancer is now to target treatments more precisely on patient's individual characteristics through precision medicine. Defects in mismatch repair, mutations in the exonuclease domain of the DNA polymerase epsilon (POLE), high tumor mutational burden and the presence of biallelic loss of CDK12 among others, are predictive biomarkers of response to immunotherapy. In the present review, we summarize the evolving landscape of immunotherapy in prostate cancer, including precision approaches and strategies to define classes of responsive patients and scale up resistance to immune checkpoint inhibitors.

2.
Expert Rev Anticancer Ther ; : 1-7, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34738499

RESUMO

BACKGROUND: Cabozantinib improves survival in metastatic renal cell carcinoma (mRCC) after prior antiangiogenics. The best treatment at disease progression (PD) is unknown. Being also a AXL/MET inhibitor, involved in acquired resistance, we hypothesized a prolonged tumor growth control in patients continuing cabozantinib despite PD. RESEARCH DESIGN AND METHODS: This retrospective multicenter study enrolled patients receiving cabozantinib after the first line between 2014 and 2020. We compared patients maintaining cabozantinib after first PD due to clinical benefit and good tolerability with those who changed therapy. The postprogression survival (PPS) of both was our primary endpoint. RESULTS: We analyzed 89 patients: 45 received cabozantinib beyond PD and 44 switched therapy. 40.4%, 31.5%, and 28.1% of patients received 1, 2, or >2 prior treatment, respectively. 84.3% were intermediate-poor International Metastatic Renal Cell Carcinoma Database risk. Patients continuing cabozantinib showed a higher response rate to cabozantinib before PD (46.7% vs 25%, p = 0.03) and were more heavily pretreated. Continuing cabozantinib showed a significantly longer PPS compared with switching therapy (median PPS 16.9 vs 13.2 months, HR 0.66, 95%CI 0.48-0.92, p = 0.011). CONCLUSIONS: We observed longer PPS in patients continuing cabozantinib beyond PD, suggesting that this could be an effective option.

3.
Cancers (Basel) ; 13(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34359706

RESUMO

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options.

4.
Cancers (Basel) ; 13(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069838

RESUMO

Active surveillance (AS) has evolved as a strategy alternative to radical treatments for very low risk and low-risk prostate cancer (PCa). However, current criteria for selecting AS patients are still suboptimal. Here, we performed an unprecedented analysis of the circulating miRNome to investigate whether specific miRNAs associated with disease reclassification can provide risk refinement to standard clinicopathological features for improving patient selection. The global miRNA expression profiles were assessed in plasma samples prospectively collected at baseline from 386 patients on AS included in three independent mono-institutional cohorts (training, testing and validation sets). A three-miRNA signature (miR-511-5p, miR-598-3p and miR-199a-5p) was found to predict reclassification in all patient cohorts (training set: AUC 0.74, 95% CI 0.60-0.87, testing set: AUC 0.65, 95% CI 0.51-0.80, validation set: AUC 0.68, 95% CI 0.56-0.80). Importantly, the addition of the three-miRNA signature improved the performance of the clinical model including clinicopathological variables only (AUC 0.70, 95% CI 0.61-0.78 vs. 0.76, 95% CI 0.68-0.84). Overall, we trained, tested and validated a three-miRNA signature which, combined with selected clinicopathological variables, may represent a promising biomarker to improve on currently available clinicopathological risk stratification tools for a better selection of truly indolent PCa patients suitable for AS.

5.
World J Urol ; 39(1): 41-47, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31776738

RESUMO

PURPOSE: In 2003, the German Cancer Society (Deutsche Krebsgesellschaft, DKG) launched a certification program aimed at improving the quality of cancer care. The purpose of this article is to describe the experience of the Prostate Cancer Unit (PCU) at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, in the process towards DKG certification. METHODS: In 2018, PCU decided to apply for certification by adopting DKG catalogue of requirements (CoR) and quality indicators. A multiprofessional working group was established with the aim of acting the necessary steps to meet DKG standards. RESULTS: Our organizational setting (procedures, personnel) and activities were accurately analyzed, thus outlining strengths and weaknesses, and modified to comply with DKG CoR and indicators. As examples, (1) a quality management plan was developed; (2) measures were taken to strengthen the surgical expertise; (3) cases evaluated in weekly tumor boards were expanded to include surgical cases with pathological risk factors, metastatic, relapsed and castration-resistant patients; (4) a survey was added to the patient-dedicated initiatives already scheduled; (5) the TuDoc software became the tool to register all new cases of prostate cancer patients referred to PCU. CONCLUSIONS: The process of certification requires many efforts but represents a unique opportunity of improving quality of care of prostate cancer patients, making it comparable on an international scale.


Assuntos
Neoplasias da Próstata/terapia , Garantia da Qualidade dos Cuidados de Saúde/normas , Idoso , Idoso de 80 Anos ou mais , Certificação , Humanos , Masculino , Pessoa de Meia-Idade
6.
Am J Clin Oncol ; 43(9): 621-627, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889831

RESUMO

OBJECTIVES: Despite the initial clinical benefit, resistance to antiangiogenic therapies develops through the activation of alternative pathways. We measured plasma levels of circulating angiogenic factors to explore their predictive role in metastatic renal cell carcinoma (mRCC) patients treated with pazopanib. MATERIALS AND METHODS: mRCC patients receiving first-line pazopanib were prospectively enrolled. The levels of circulating interleuchine (IL)-6, IL-8, stromal derived factor-1, vascular endothelial growth factor-A, hepatocyte growth factor (HGF), osteopontin, and E-selectin were quantified at baseline and every 4 weeks until disease progression (PD). Patients were dichotomized into "low" and "high" subgroups by a cutoff point defined by the respective median circulating angiogenic factor (CAF) value at baseline. Then, association with the objective response was determined. Changes in CAF levels between baseline and PD were also compared. RESULTS: Among 25 patients included in the final data set, 6 patients were still on treatment. As best response, 12 patients presented a partial response (48%), 9 showed stable disease, and 4 showed PD. The median follow-up was 31.9 months. The median progression-free survival was 14.8 months. Low baseline levels of IL-6, IL-8, HGF, and osteopontin were found to be significantly associated with objective response. In addition, patients with low baseline levels of HGF showed longer progression-free survival and overall survival, whereas patients with low baseline levels of IL-8 showed longer overall survival. Among patients experiencing PD, the median plasma levels of stromal derived factor-1 and vascular endothelial growth factor-A were significantly higher compared with the baseline (P=0.01; P=0.011). Conversely, the median levels of E-selectin were significantly lower compared with the baseline (P=0.017). CONCLUSION: Changes in levels of selected CAFs were associated with response/resistance to pazopanib in mRCC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/secundário , Quimiocina CXCL12/sangue , Progressão da Doença , Selectina E/sangue , Feminino , Fator de Crescimento de Hepatócito/sangue , Humanos , Indazóis , Interleucina-6/sangue , Interleucina-8/sangue , Neoplasias Renais/sangue , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Osteopontina/sangue , Intervalo Livre de Progressão , Estudos Prospectivos , Critérios de Avaliação de Resposta em Tumores Sólidos , Taxa de Sobrevida , Fator A de Crescimento do Endotélio Vascular/sangue
7.
Front Oncol ; 10: 1644, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903369

RESUMO

Introduction: In the last decades, the therapeutic decision-making approach to metastatic renal cell cancer (mRCC) has dramatically changed thanks to the introduction in the treatment scenario of, first, anti-angiogenic agents and, afterward, immune-checkpoint inhibitors (ICIs). Immunotherapy is now the standard of care in pretreated mRCC patients and has recently entered even the first line setting. Nevertheless, in mRCC as well as in other tumor settings, a durable and clinically meaningful benefit from treatment with ICIs is not obtained for all patients treated. Therefore, the necessity to identify and validate predictive biomarkers of response to immunotherapy has emerged, in order to design the optimal treatment strategy for mRCC patients. Discussion: In this review, we present and discuss the most promising predictive biomarkers of response to ICIs in mRCC with the recent data available. In details, the first marker that was investigated is the immunohistochemical expression of programmed death receptor ligand 1 (PD-L1), showing a negative prognostic role in mRCC, but the debate about its potential predictive value is still open. Additionally, the high heterogeneity in PD-L1 determination methods adds complexity to this issue. Second, the tumor mutational or neoantigen burden is an emerging biomarker of increased response to immunotherapy, hypothesizing that the higher the TMB, the higher is the production of neoantigens, and thus the stimulation of anti-tumor immune response, even though controversial results have been obtained. Third, the tumor microenvironment, namely the different populations of the immune infiltrate, plays a key role in tumor progression and in the response to immunotherapy. Finally, several studies have collected evidence on the potential association of the occurrence of immune-related adverse events (irAEs) with the benefit from ICIs, first in non-small cell lung cancer (NSCLC) and melanoma, and recently even in mRCC. Conclusion: Several promising biomarkers of response to immunotherapy with ICIs have been identified, though without conclusive results upon their potential predictive value in mRCC. Therefore, the results of the exploratory analyses of the recently presented first-line trials and hopefully of future prospective, biomarker-driven studies could provide useful tools to be applied in the everyday clinical practice.

8.
Expert Rev Anticancer Ther ; 20(8): 715-726, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32758032

RESUMO

INTRODUCTION: In prostate cancer , there has recently been an emerging interest in mutations in genes belonging to the homologous recombination repair (HRR) pathway and in the inhibition of poly (ADP-ribose) polymerase (PARP) proteins. AREAS COVERED: Mutations in the HRR genes, including BRCA1, BRCA2, and Ataxia-Telangiesctasia mutated (ATM), have been reported in prostate cancer, with different incidence in the localized and advanced settings. The PARP enzyme complex is involved in repair of DNA damage and its inhibition causes the accumulation of DNA mutations in HRR deficient cells. Several PARP inhibitors (PARPi) are under development, such as olaparib, talazoparib, niraparib, rucaparib, and veliparib. In metastatic castration resistant prostate cancer (mCRPC), olaparib has been the most studied and its clinical efficacy has been validated in a phase III clinical trial. Rucaparib and niraparib have also shown promising results in the preliminary analyzes of two phase II trials, while talazoparib is currently under development. EXPERT OPINION: PARPi have become part of the treatment of mCRPC. Early results of combination therapy with PARPi and new hormonal therapy are promising and are supported by a strong biological rationale. Current results need to be validated in randomized phase III-controlled trials in order to translate the use of PARPi into real world practice.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Animais , Reparo do DNA/genética , Desenvolvimento de Medicamentos , Humanos , Masculino , Mutação , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia
9.
Cancer Treat Rev ; 88: 102057, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32574991

RESUMO

Despite advances in metastatic prostate cancer therapy, expected survival for patients in the castration-resistant phase of disease is poor. Immune-checkpoints inhibitors significantly prolonged life expectancy in some solid tumors and have been evaluated also in advanced stage prostate cancer. The majority of data available derive from preliminary phase I and II trials evaluating CTLA-4 and PD-1 as monotherapy or in combination with each other, vaccines, radiotherapy or targeted/hormonal therapy, achieving only limited benefits in terms of biochemical and radiologic responses. There are many reasons that may explain why prostate cancer responds poorly to modern immunotherapies, such as its characteristic low tumor mutational burden or immune-suppressive tumor microenvironment. The present review summarizes the results obtained treating advanced prostate cancer patients with immune-checkpoints inhibitors and analyzes potential mechanisms of both resistance and sensitivity, in order to hypothesize possible avenues of special interest for future research.


Assuntos
Imunoterapia/métodos , Neoplasias de Próstata Resistentes à Castração/terapia , Antineoplásicos Imunológicos/administração & dosagem , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Vacinas Anticâncer/administração & dosagem , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Masculino , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
J Clin Med ; 9(4)2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32231117

RESUMO

The frontline treatment options for patients with metastatic renal cell carcinoma (mRCC) are evolving rapidly since the approval of combination immunotherapies by the U.S. Food and Drug Administration (USFDA) and the European Medicines Agency (EMA). In particular, in combination with vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) have significantly improved the outcome of patients with mRCC compared to TKI monotherapy. Here, we review the preclinical data supporting the combination of ICIs with VEGFR TKIs. The VEGF-signaling inhibition could ideally sustain immunotherapy through a positive modulation of the tumor microenvironment (TME). Antiangiogenetics, in fact, with their inhibitory activity on myelopoiesis that indirectly reduces myeloid-derived suppressor cells (MDSCs) and regulatory T cells' (Tregs) frequency and function, could have a role in determining an effective anti-tumor immune response. These findings are relevant for the challenges posed to clinicians concerning the clinical impact on treatment strategies for mRCC.

11.
Tumori ; 106(5): 406-412, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32116138

RESUMO

INTRODUCTION: Therapeutic decision-making in metastatic castration-resistant prostate cancer (mCRPC) represents an open challenge. Radium-223 is approved for patients with symptomatic bone metastases, no visceral involvement, progressing after at least 2 lines of systemic therapy, or ineligible for any other systemic treatment. METHODS: We performed a retrospective, observational study on patients with mCRPC treated with radium-223 at our institution outside of clinical trials, to assess the safety and activity in a real-world population. Data regarding baseline patient/disease characteristics and treatment outcomes (number of cycles, treatment-related adverse events [AEs], cause of discontinuation, and best response) were collected. RESULTS: Overall, 41 patients were treated from September 2015 to September 2018. Median age was 73 years; baseline Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 0, 1, or 2 in 15%, 80%, and 5% of cases, respectively; and 3%, 41%, 44%, and 12% of patients had <6, 6-20, >20, and superscan bone lesions, respectively. A median number of 5 cycles (interquartile range 3-6) with median dose 19.52 MBq (interquartile range 12.87-24.83) was received. Treatment schedule was completed in 49% of cases; discontinuations due to AEs, disease-related death, or disease progression occurred in 24%, 33%, and 43% of patients, respectively. Any-grade AEs occurred in 73% and grade 3/4 treatment-related AEs occurred in 29% of patients, mainly anemia, decreased platelet count, and fatigue. No skeletal-related events or treatment-related deaths were recorded. After treatment, 66%, 2%, and 32% of patients had a stable, improved, or deteriorated ECOG PS versus baseline, respectively, and 24%, 61%, and 15% reported a stable, improved, or worsened pain symptom control. Post-treatment versus baseline alkaline phosphatase was reduced or stable in 46% and increased in 54% of patients, whereas prostate-specific antigen was decreased or stable in 83% and increased in 17% of patients. CONCLUSIONS: Our study provides clinically useful real-world data on radium-223, highlighting the importance of multidisciplinary patient management to guarantee the best continuum of care for patients with mCRPC.


Assuntos
Neoplasias de Próstata Resistentes à Castração/radioterapia , Radioisótopos/uso terapêutico , Rádio (Elemento)/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Neoplasias de Próstata Resistentes à Castração/patologia , Radioisótopos/efeitos adversos , Rádio (Elemento)/efeitos adversos , Resultado do Tratamento
12.
Int J Mol Sci ; 21(4)2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32098246

RESUMO

Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix™ approach for CTC-enrichment coupled with positive and negative selection with the DEPArray™ with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold ≥1CTC/10 mL of blood, the positivity rates were 28% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Deleção Cromossômica , Cromossomos Humanos Par 9/genética , Neoplasias Renais , Células Neoplásicas Circulantes , Análise de Célula Única , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia
13.
Curr Oncol Rep ; 22(1): 9, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989430

RESUMO

PURPOSE OF REVIEW: The aim of this review is to sum up the state of the art of urachal carcinoma (UC) in order to easily guide clinicians. RECENT FINDINGS: UC is a rare and aggressive disease with consequent few data about diagnosis and treatment. Dates are mainly based on retrospective trial and case reports with limited prospective trial. Clinical presentation is not specific, often with urinary symptoms. Diagnosis is mainly based on CT scan and MRI, useful to evaluate local invasion and nodal status and to detect the presence of distant metastases. Therefore, biopsy is needed to obtain histological confirmation. Surgery is the gold standard for localized disease, while different chemotherapy schemes have been used in metastatic setting. Novel findings based on mutational analysis of the tumor include the use of biological treatment, such as cetuximab, and immunotherapy, such as atezolizumab, with satisfactory responses, suggesting that personalized treatment could be the most suitable option for UC.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Adenocarcinoma/patologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante , Cistectomia/métodos , Humanos , Imunoterapia , Terapia de Alvo Molecular , Prognóstico , Neoplasias da Bexiga Urinária/patologia
14.
Int J Mol Sci ; 20(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480348

RESUMO

Immunotherapy has changed the therapeutic scenario of metastatic renal cell carcinoma (mRCC), however the evaluation of disease response to immune-checkpoint inhibitors is still an open challenge. Response evaluation criteria in solid tumors (RECIST) 1.1 criteria are the cornerstone of response assessment to anti-neoplastic treatments, but the use of anti-programmed death receptor 1 (PD1) and other immunotherapeutic agents has shown atypical patterns of response such as pseudoprogression. Therefore, immune-modified criteria have been developed in order to more accurately categorize the disease response, even though their use in the everyday clinical practice is still limited. In this review we summarize the available evidence on this topic, with particular focus on the application of immune-modified criteria in the setting of mRCC.


Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Imunoterapia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Padrões de Prática Médica , Carcinoma de Células Renais/imunologia , Humanos , Neoplasias Renais/imunologia , Metástase Neoplásica , Critérios de Avaliação de Resposta em Tumores Sólidos
15.
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
16.
Cancer Treat Rev ; 79: 101891, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31491662

RESUMO

Collecting ducts carcinoma (CDC) is a rare and aggressive histological subtype of renal cancer accounting for only 1% of renal tumors. Usually patients present in bad clinical conditions due to a symptomatic disease with synchronous metastasis. Due to the rarity of CDC, data from prospective trials evaluating the best treatment for these patients are limited. The prognosis is poor with a median overall survival of around 11 months for patients with metastatic disease. The best treatment option today is considered a doublet chemotherapy with platinum salt plus gemcitabine as a result from a prospective phase II trial, but survival outcomes remain unsatisfactory. The interest in the in-depth understanding the biology of this orphan disease is growing, leading to find potential new biological-driven treatment approaches. Here we review the up-to-date literature evidences to address the best management of this rare and unfavorable clinical condition.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/terapia , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Animais , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/mortalidade , Terapia Combinada , Gerenciamento Clínico , Humanos , Neoplasias Renais/etiologia , Neoplasias Renais/mortalidade , Prognóstico , Resultado do Tratamento
19.
Cancers (Basel) ; 11(7)2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31337040

RESUMO

Enzalutamide and abiraterone have been shown to improve progression-free survival (PFS) and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients. Moreover, some patients may not benefit from the inhibition of androgen receptor (AR) activity or, alternatively, may develop secondary resistance. Detection in patients' circulating tumor cells (CTCs) of ARV7, a splicing variant of AR lacking the ligand-binding domain, showed a link with treatment failure. Independent confirmation of the predictive role of CTC status combined with ARV7 detection is, therefore, a priority for extending personalized biomarker-driven treatments to all patients. In this prospective observational study, CTC status and the expression of AR and ARV7 were measured in 37 mCRPC patients, before starting treatment with enzalutamide or abiraterone, by employing commercially available kits. CTC status was positive in 21/37 patients: 46% and 24% of CTC-positive patients were defined as AR- and ARV7-positive, respectively. Kaplan-Meier estimates showed that positivity for each variable was significantly associated with poorer radiological PFS, PSA-PFS, and OS. All considered treatment outcomes worsened when going from CTC-negative to CTC-positive/ARV7-negative to CTC-positive/ARV7-positive patients, both in the global case series and in patients stratified into three groups based on basal PSA levels. Presently, technical approaches appear to be mature for introducing CTC/ARV7 tests in clinical practice.

20.
Expert Rev Anticancer Ther ; 19(7): 603-611, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31159619

RESUMO

Introduction: So far, clinical experiences have proved metastasectomy as the only approach in the setting of metastatic renal cell carcinoma that may achieve the 'no evidence of disease' status, with an associated improvement in survival. Areas covered: This review aims to summarize the body of knowledge on therapeutic approaches to mRCC, with a specific insight on the role of metastasectomy and on which underlying factors could be good predictors to select patients who may benefit from surgery. In detail, we managed to identify as potential selection criteria: the number of lesions and their site, the DFI, patients' performance status and, most of all, the completeness of resection. Expert opinion: The definition of the optimal treatment strategy of mRCC patients is still an unmet clinical need. The decision-making process about treatment strategy should consider specific tumor's and patient's characteristics, as well as the integration of the available therapeutic approaches with the aim to reach the best clinical outcome. We consider multidisciplinary management mandatory in order to tailor the treatment approach according to the patient and disease features. The experience of clinicians may be considered crucial in order to select the best candidates for a multimodal approach.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Metastasectomia/métodos , Tomada de Decisões , Humanos , Metástase Neoplásica , Seleção de Pacientes
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