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1.
J Bone Oncol ; 31: 100405, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34934613

RESUMO

Bone metastases are common in genitourinary cancers, but they are underreported and not well researched. Synchronous bone metastases occur in 1.39-5.5% of bladder cancer patients, while 30-40% of cases are metachronous. Bone morphogenetic proteins (BMPs) play a key role in regulating proliferation, migration and invasion of tumor cells in bone microenvironment of bone metastases from metastatic urothelial carcinoma (mUC). Bone metastases represent a poor prognostic factor due to high morbidity and mortality correlated to skeletal-related events (SREs). The incidence rate of SREs in bladder, renal pelvis, and ureteral cancer varies from 39 to 68%. Radiotherapy is the most frequent treatment for SREs. The early use of bone targeted therapies (BTT), zoledronic acid and denosumab, improves SREs incidence and morbidity and it seems to improve overall survival (OS). To date, several new agents (immunotherapy and targeted drugs) demonstrated efficacy in mUC. However, subgroup analysis for bone metastases is often not available, due to difficulties in analysing bone samples, non-RECIST lesions and delay in systemic treatment due to SREs that limit the enrolment of bone mUC patients in clinical trials. Larger solid tumor studies that included UC patients are the main source of data for the management of mUC patients with bone metastases. For these patients, multidisciplinary approach should be preferred, involving orthopaedics, radiotherapists and rehabilitation to improve outcome and quality of life. New prospective trials should characterize clinical and molecular features of patients with bone metastases and the impact of new drugs on this poor prognostic metastatic site.

2.
Front Oncol ; 10: 565857, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072597

RESUMO

Currently, renal cell carcinoma is characterized by encouraging benefits from immunotherapy that have led to significant results in treatment outcome. The approval of nivolumab primarily as second-line monotherapy and, more recently, the approval of new combination therapies as first-line treatment have confirmed the importance of immunotherapy in this type of tumor. In this context, the chimeric antigen receptor (CAR)-T represents a further step forward in the field of immunotherapy. Initially tested on hematological malignancies, this new therapeutic approach is also becoming a topic of great interest for solid tumors. Although the treatment has several advantages over previous T-cell receptor-dependent immunotherapy, it is facing some obstacles in solid tumors such as a hostile tumor microenvironment and on-tumor/off-tumor toxicities. Several strategies are under investigation to overcome these problems, but the approval of CAR-T cell therapy is still some way off. In renal cancer, the significant advantages obtained from immune checkpoint inhibitors represent a good starting point, but the potential nephrological toxicity of CAR-T cell therapy represents an important risk. In this review, we provide the rationale and preliminary results of CAR-T cell therapy in renal cell malignancies.

3.
Front Oncol ; 10: 1325, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32923384

RESUMO

High-dose chemotherapy (HDCT) has curative potential in relapsed/refractory germ cell tumors (GCT). Due to the complexity of this population and the toxicity of HDCT, we evaluated the association between blood-based systemic inflammatory indexes and the outcome of GCT patients undergoing salvage treatment with HDCT in order to define additional prognostic factors able to orient clinical decision. Baseline characteristics, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) of 62 patients undergoing HDCT for GCT were retrospectively collected. The aim is to evaluate the correlation between each inflammatory marker (NLR, PLR, and SII) and response to HDCT, overall survival (OS), and progression-free survival (PFS). Using the receiver operating curve to identify the best cutoff values, it was found that patients with GCT with NLR ≥3.3 and SII ≥844,000 had shorter PFS and inferior OS. In the multivariable analysis including inflammatory markers, the International Prognostic Factor Study Group (IPFSG) risk group, age, and previous line of treatment, NLR ≥3.3 and SII ≥844,000 were identified to be independently associated with shorter PFS and OS. Moreover, NLR, PLR, and SII significantly correlate with overall response to HDCT. Associating IPFSG prognostic score to inflammatory markers at baseline of HDCT may improve prognostic information and could help physicians to make more personalized treatment decisions.

4.
J Clin Med ; 9(6)2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32580478

RESUMO

Androgen deprivation therapy (ADT) is a cornerstone of treatment for prostate cancer and, in recent years, androgen receptor (AR)-targeted therapies (abiraterone and enzalutamide) have both been used for the treatment of castration-resistant prostate cancer (CRPC). In our study, we sought to investigate the association between ADT and immune disorders, considering a potential role of androgens in the immune modulation. We retrospectively evaluated CRPC patients treated with abiraterone/enzalutamide between July 2011 and December 2018. We assessed the risk of developing immune alterations and their impact on outcome. We included 844 CRPC patients receiving AR-directed therapies, of whom 36 (4.3%) had autoimmune diseases and 47 (5.6%) second tumors as comorbidities. Median age was 70 years [interquartile range (IQR) = 63-75)]. We showed higher significant incidence of autoimmune diseases during their hormone sensitive status (p = 0.021) and the presence of autoimmune comorbidities before starting treatment with abiraterone/enzalutamide was significantly associated with worse overall survival (OS) (10.1 vs. 13.7 months, HR = 1.59, 95% CI 1.03-2.27, p = 0.038). In a multivariate analysis, the presence of autoimmune disorders was an independent predictor of OS (HR = 1.65, 95% CI 1.05-2.60, p = 0.031). In conclusion, CRPC patients with autoimmune alterations before starting AR-directed therapies may have worse prognosis. Further prospective studies are warranted to assess the role of immune modulation in the management of prostate cancer patients.

5.
Oncotarget ; 11(10): 924-941, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32206189

RESUMO

Pancreatic cancer is one of the leading causes of cancer death worldwide. Its high mortality rate has remained unchanged for years. Radiotherapy and surgery are considered standard treatments in early and locally advanced stages. Chemotherapy is the only option for metastatic patients. Two treatment regimens, i. e. the association of 5-fluorouracil- irinotecan-oxaliplatin (FOLFIRINOX) and the association of nab-paclitaxel with gemcitabine, have been shown to improve outcomes for metastatic pancreatic adenocarcinoma patients. However, there are not standardized predictive biomarkers able to identify patients who benefit most from treatments. CA19-9 is the most studied prognostic biomarker, its predictive role remains unclear. Other clinical, histological and molecular biomarkers are emerging in prognostic and predictive settings. The aim of this review is to provide an overview of prognostic and predictive markers used in clinical practice and to explore the most promising fields of research in terms of treatment selection and tailored therapy in pancreatic cancer.

6.
Anticancer Drugs ; 31(3): 314-318, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31929349

RESUMO

In metastatic renal cell carcinoma (mRCC) patients, cardiac metastases are a rare and often a post-mortem finding. Clinical manifestations of cardiac metastases have a late onset and include pericardial effusions, heart failure and embolic phenomena. Treatment of cardiac metastasis is not yet standardized, and few data are available about the efficacy of TKI on treatment of cardiac metastases in mRCC patients. In this report, we describe the case of a 66-year-old male who presented with mRCC with lung and cardiac metastases treated with cabozantinib, a multikinase inhibitor that was administered in second line after disease progression with sunitinib. To date, there are no data about the safety and efficacy of cabozantinib in mRCC with cardiac metastasis. In a real word analysis, cabozantinib demonstrated to be associated to a modest risk of developing left ventricular heart failure. It is unknown if this risk is higher in mRCC population with cardiac metastases. We report the first evidence of efficacy and safety of cabozantinib in cardiac mRCC patients, probably due to its specific inhibition of several molecular intracellular pathways. Additional molecular and clinical studies are needed before well tolerated and efficacy of cabozantinib treatment for these patients can be fully understood.


Assuntos
Anilidas/uso terapêutico , Carcinoma de Células Renais/patologia , Neoplasias Cardíacas/tratamento farmacológico , Neoplasias Cardíacas/secundário , Neoplasias Renais/patologia , Piridinas/uso terapêutico , Idoso , Anilidas/efeitos adversos , Humanos , Masculino , Piridinas/efeitos adversos
7.
Ther Adv Med Oncol ; 11: 1758835919890285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803255

RESUMO

Inhibitors of fibroblast growth factor receptor (FGFR) represent an outstanding treatment approach for selected patients with urothelial cancer (UC). These agents are changing the clinical approach to a subgroup of UC, the luminal-papillary subtype, characterized by FGFR mutations, fusions, or amplification. In this review, we provide an overview of the results of recent clinical trials on FGFR tyrosine kinase inhibitors (TKIs) currently in clinical development for the treatment of UC: erdafitinib, rogaratinib, infigratinib, and the monoclonal antibody vofatamab. The Food and Drug Administration recently granted accelerated approval to erdafitinib for patients with advanced UC with alterations of FGFR2 or FGFR3 after progression on platinum-based chemotherapy. We also look at future therapeutic options of combination regimens with immune-checkpoint inhibitors as strategies for improving the antitumor effects of this class of drug, and for preventing or delaying the development of resistance.

8.
J Immunother Cancer ; 7(1): 258, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619289

RESUMO

Prostate cancer (PCa) is one of the main causes of cancer-related death in men. In the present immunotherapy era, several immunotherapeutic agents have been evaluated in PCa with poor results, possibly due to its low mutational burden. The recent development of chimeric antigen receptor (CAR)-T cell therapy redirected against cancer-specific antigens would seem to provide the means for bypassing immune tolerance mechanisms. CAR-T cell therapy has proven effective in eradicating hematologic malignancies and the challenge now is to obtain the same degree of in solid tumors, including PCa. In this study we review the principles that have guided the engineering of CAR-T cells and the specific prostatic antigens identified as possible targets for immunological and non-immunological therapies. We also provide a state-of-the-art overview of CAR-T cell therapy in PCa, defining the key obstacles to its development and underlining the mechanisms used to overcome these barriers. At present, although there are still many unanswered questions regarding CAR-T cell therapy, there is no doubt that it has the potential to become an important treatment option for urological malignancies.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias da Próstata/terapia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/transplante , Humanos , Imunoterapia Adotiva/tendências , Masculino , Neoplasias da Próstata/imunologia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Literatura de Revisão como Assunto , Linfócitos T/imunologia , Linfócitos T/metabolismo , Microambiente Tumoral/imunologia
9.
J Oncol ; 2019: 7317964, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31641355

RESUMO

Immunotherapy represents the new era of cancer treatment because of its promising results in various cancer types. In urological tumors, the use of the immune-checkpoint inhibitors (ICIs) is increasingly spreading. Although not all patients and not all diseases respond equally well to immunotherapy, there is an increasing need to find predictive markers of response to ICIs. Patient- and tumor-related factors may be involved in primary and secondary resistance to immunotherapy: tumor-derived protein and cytokines, tumor mutational burden, and patient performance status and comorbidities can condition tumor response to ICIs. Recently, some of these factors have been evaluated as potential biomarkers of response, with conflicting results. To date, the expression of programmed death-ligand 1 (PD-L1) and the presence of deficient mismatch repair (dMMR) in tumor tissue are the only biomarkers capable of guiding the clinician's decision in urothelial cancer and prostate cancer, respectively. In this review, we performed a comprehensive search of the main publications on biomarkers that are predictive of response to ICIs in urological cancers. Our aim was to understand whether existing data have the potential to drive clinical decision-making in the near future.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31191451

RESUMO

Testicular cancer is the most common tumor in young males aged 15-40 years. The overall cure rate for men with testicular cancer is >90%, so a huge number of these patients will become testicular cancer survivors. These people may feel some stress in the experience of diagnosis, treatment, and consequences that affects the quality of life, and during follow-up, especially when new issues and emotional distresses appear over time, such as late side-effects of treatments and emotional challenges including fear of tumor relapse, fertility and sexuality concerns, and social and workplace issues. The cancer experience has an impact not only on patients, but also on their relatives (e.g., spouses, parents, or siblings), who often have to assume a caregiving role for the duration of and following treatment for cancer. Moreover, the caregiver plays an important role in supporting a man with a testicular cancer, providing physical and emotional care. This review presents a summary of existing knowledge regarding the impact and the burden of testicular cancer on caregivers.

13.
Oncotarget ; 9(61): 31877-31887, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30159129

RESUMO

BACKGROUND: The present analysis focuses on real-world data of Everolimus-Exemestane in advanced HR+ve, HER2-ve elderly breast cancer patients (aged 65 years) included in the EVA study, with unique findings in those aged 70 years. METHODS: Data are collected from clinical records and analysed according to age cut-off (< 65 years; 65 - 69 years and {greater than or equal to} 70 years). Relationship of analyzed variables with response were tested by mean of a Mantel-Haenszel chi square test. Time to event analysis was described by Kaplan Meier approach and association with baseline characteristics was analysed by stratified log-rank test and proportional hazard model. RESULTS: From July 2013 to December 2015, the EVA study enrolled overall 404 pts. 154 patients out of 404 (38,1%) were aged {greater than or equal to} 65 years, of whom 87 were {greater than or equal to} 70 years. Median duration of EVE treatment was 28.5 weeks (95% CI 19.0 - 33.8) in patients aged 65-69 years and 24,4 weeks (95% CI 19,2 - 33,2) in those aged {greater than or equal to} 70 years. Fewer patients aged 65 years received the highest EVE Dose-Intensity (>7.5 mg/day) in comparison to younger patients (49,6% vs. 66,8%). Grade 3-4 toxicities occurred to 55 patients (35,7%), mainly stomatitis (10,9%), rash (5,8%) and non-infectious pneumonitis (NIP) (3,6%). Some toxicities, such as weight loss and anaemia were peculiarly observed in patients aged {greater than or equal to} 70 years. Five treatment-related deaths were collected (3,2%). CONCLUSIONS: EVE-EXE combination remains one of the potential treatments in HR+ patients also for elderly ones.

15.
Drugs Aging ; 32(3): 235-41, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25721557

RESUMO

BACKGROUND: The use of oral anticoagulant therapy (OAT) has constantly increased in the prevention of thromboembolism, particularly in patients 80 years of age or older. OBJECTIVE: The aim of this multicentre study was to evaluate the efficacy and safety of vitamin K antagonists (VKAs) in elderly patients managed with a computer dosing algorithm compared with a dosage decided by expert physicians. MATERIALS AND METHODS: Nine Italian thrombosis centres utilising the Zeus dosing algorithm were involved. The before-after study enrolled patients managed firstly by medical staff (manual system) or with the PARMA algorithm for 12 months from July 2008 to June 2009 and then with the Zeus algorithm during the analogous period from 2010 to 2011. Of 7605 patients in the OAT maintenance phase, 2281 were older than 80 years (mean age 84.2 years). Data for these 2281 patients managed with both modalities were analysed. RESULTS: Of the 2281 patients 80 years of age or older, 1776 underwent OAT for atrial fibrillation (AF). Use of a dosing algorithm increased the OAT quality: time in therapeutic range (TTR) was significantly (p < 0.001) higher during the Zeus period than during the manual period (71.6 vs. 68.8 %). The TTR achieved with Zeus was similar to that obtained with the PARMA algorithm. In addition, patients managed with Zeus took a weekly drug dosage significantly (p < 0.01) lower than that both suggested by PARMA and prescribed by expert physicians, with a reduced number of adverse events. CONCLUSIONS: This study confirms that the effectiveness and safety of VKA therapy in patients 80 years of age or older increases with computer dosing algorithms.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Tromboembolia/prevenção & controle , Vitamina K/antagonistas & inibidores , Idoso de 80 Anos ou mais , Algoritmos , Anticoagulantes/administração & dosagem , Feminino , Humanos , Masculino , Estudos Retrospectivos , Trombose/prevenção & controle
16.
Tumori ; 99(6): 273e-7e, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24503802

RESUMO

This report describes a case of ab initio metastatic HER2-positive breast cancer in a very young patient. The onset of breast cancer at such a young age is uncommon and could delay the diagnosis with unquestionable impact on the prognosis. Unfortunately, the patient experienced cerebral progression during first-line treatment. Indeed, brain metastases occur in about one-third of HER2-positive metastatic breast cancer patients during trastuzumab-based treatment. The small molecule lapatinib is active in established cerebral disease, and we report a complete brain response longer than expected, thanks to a well-tolerated, orally administered combination of lapatinib and capecitabine.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias Ósseas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptor ErbB-2/análise , Administração Oral , Adulto , Neoplasias Ósseas/complicações , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias Encefálicas/diagnóstico , Neoplasias da Mama/química , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Lapatinib , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Dor/etiologia , Quinazolinas/administração & dosagem , Resultado do Tratamento
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