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1.
Artigo em Inglês | MEDLINE | ID: mdl-34802383

RESUMO

INTRODUCTION: Immune checkpoint inhibitor (ICI) monotherapy appears to be effective in a small cohort of patients with metastatic triple negative breast cancer (mTNBC). This supports the exploration of strategies for increasing the efficacy of immunotherapy. To enhance overall response and clinical outcomes, several immune-based combinations are being investigated. AREAS COVERED: The authors present a synopsis of current, state of art immune-based combinations in this setting and reflect on future possibilities. They shed light on recently presented and published clinical trials and ongoing studies. A literature search was conducted in October 2021; in addition, abstracts of international cancer meetings were reviewed. EXPERT OPINION: Clinical trials suggest that ICI monotherapy could be beneficial in a minority of mTNBC patients; conversely, several immune-based combinations have reported notable results in recently presented or published studies. Some of these combination strategies have been approved for mTNBC - as in the case of chemoimmunotherapy in PD-L1 positive patients. Numerous trials are investigating novel ICI-based combinations and their results are eagerly awaited.

2.
Curr Oncol ; 28(5): 3393-3402, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34590592

RESUMO

Ampullary carcinomas (ACs) represent a rare entity, accounting for approximately 0.2% of all gastrointestinal solid tumors and 20% of all periampullary cancers (PACs). Unfortunately, few data are available regarding the optimal therapeutic strategy for ACs due to their rarity, and physicians frequently encounter significant difficulties in the management of these malignancies. In this review, we will provide an overview of current evidence on AC, especially focusing on biological features, histological characteristics, and available data guiding present and future therapeutic strategies for these rare, and still barely known, tumors.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Neoplasias do Ducto Colédoco/terapia , Humanos
4.
Expert Opin Drug Metab Toxicol ; 17(10): 1237-1243, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34407702

RESUMO

Background: With hormonal agents quickly expanding as novel therapeutic options in nonmetastatic castration-resistant prostate cancer (nmCRPC), the toxicity profile of enzalutamide, apalutamide, and darolutamide should be kept in mind.Methods: We performed an updated meta-analysis with the aim to analyze the risk of treatment-related cardiovascular (CV) events, any grade, and grade 3-4 (G3-4) hypertension in nmCRPC patients treated with enzalutamide, apalutamide, and darolutamide plus androgen deprivation therapy (ADT) versus ADT plus placebo in randomized controlled trials (RCTs). Results were compared by calculating Relative Risk (RR) with 95% confidence intervals (CIs); RRs were combined with Mantel-Haenszel method.Results: Three RCTs involving 4110 patients were available for the meta-analysis. According to our results, the addition of novel hormonal agents was associated with a significantly increased risk of CV events (RR = 1.71; 95% CI 1.29-2.27) and G3-4 hypertension (RR = 1.53; 95% CI 1.19-1.97). In addition, a trend toward a higher risk of any grade hypertension was reported in the experimental arm.Conclusions: The use of enzalutamide, apalutamide, and darolutamide in nmCRPC patients implies a careful benefit-risk assessment. Real-world, large-cohort studies are warranted to confirm the findings of our meta-analysis.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Hipertensão/induzido quimicamente , Antagonistas de Receptores de Andrógenos/administração & dosagem , Antagonistas de Receptores de Andrógenos/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Humanos , Hipertensão/epidemiologia , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Expert Rev Gastroenterol Hepatol ; 15(11): 1245-1251, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34431725

RESUMO

INTRODUCTION: Immunotherapy has recently taken on an extremely important role in medical oncology, as first- or later-line treatment in several tumor types, and recent years have seen the emerging of clinical trials assessing immune checkpoint inhibitors (ICIs) in unresectable hepatocellular carcinoma (HCC). AREAS COVERED: Herein, we provide an overview of recently published studies exploring the dual immune checkpoint blockade or the combination of ICIs plus biological treatments as first-line treatment in HCC patients with advanced disease, especially focusing on the biological rationale behind these therapeutic strategies, and ongoing active and recruiting clinical trials. EXPERT OPINION: Results of studies on monotherapy with ICIs have suggested that this strategy could be beneficial only in a minority of patients; conversely, the recently published IMbrave150 study has reported an overall survival benefit in HCC receiving the combination of atezolizumab plus bevacizumab compared to sorafenib as first-line treatment. A wide number of clinical trials is evaluating ICI-based combinations in advanced HCC, a strategy which is supported by robust preclinical and early-phase clinical data, and results of these studies are highly awaited.

7.
Anticancer Res ; 41(6): 2759-2772, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34083266

RESUMO

The intestinal microbiota, which has gained a foothold in the field of research, represents a significant factor for human health because of its ability to form relationships with the organism through the modulation of pathophysiological processes. Dysbiosis, which is caused by non-specific intestinal inflammation and leads to a condition of persistent low-grade inflammation, may be caused by poor eating habits and an unhealthy lifestyle, as well as psycho-physical stress and a sedentary lifestyle. Diet, prebiotics and probiotics, and moderate and aerobic exercise can, in order to increase well-being and reduce the chance of recurrence, all be deemed effective methods of improving gut-microbiota pretreatment or mitigating diseases or dysbiosis. This study shows the ways in which good living habits, correct nutrients, and constant aerobic activity in chronic and immune conditions, can modify gut microbiota and microbiome characteristics, as well as the relationship between intestinal function and human health.


Assuntos
Dieta , Exercício Físico , Microbioma Gastrointestinal , Probióticos , Humanos , Derivados da Hipromelose
8.
Expert Opin Investig Drugs ; : 1-8, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34167433

RESUMO

Introduction: While sorafenib monotherapy represented the mainstay of medical treatment for advanced hepatocellular carcinoma (HCC) patients for more than a decade, novel agents and combination therapies have recently produced unprecedented paradigm shifts. The combination of lenvatinib plus pembrolizumab is now being evaluated as a front-line treatment in advanced HCC patients; early phase clinical trials have already reported promising results.Areas covered: This paper reviews the combination of lenvatinib plus pembrolizumab for the treatment of advanced HCC. The preclinical rationale and completed and ongoing trials are examined and later, the authors reflect on biomarkers of predictive of response to immune-based combinations and future treatment decision-making on the basis of tolerability and clinical benefits provided by these novel therapeutics. A literature search was conducted in April 2021 of Pubmed/Medline, Cochrane library and Scopus databases; moreover, abstracts of international cancer meetings were reviewed.Expert opinion: The landscape of new agents and combinations continues to expand. Recently, immune-based combinations have reported important results in advanced HCC, as witnessed by the landmark IMbrave150 trial. Based on the promising results of early phase clinical trials, lenvatinib plus pembrolizumab has the potential to represent a novel treatment option in this setting.

9.
Future Oncol ; 17(8): 955-963, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33538176

RESUMO

Metaplastic breast cancer (MPBC) is a rare and aggressive tumor type in great need of satisfactory therapies. Although most cases of MPBC are 'triple negative', they are nonetheless related to worse outcomes compared with other triple-negative invasive tumors. MPBC presents high levels of genetic and molecular heterogeneity, suggesting that novel targeted therapies can be exploited. Overexpression of PD-L1 and high levels of tumor-infiltrating lymphocytes have also been observed in these tumors, suggesting a role for immunotherapy. We present an updated literature revision on clinical, histopathological and molecular features of MPBC and their significance to prognosis and therapy options. We discuss emerging efforts to improve and personalize prognostic and therapeutic approaches, exploiting the molecular signature of MPBC with targeted therapies and immunotherapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/terapia , Heterogeneidade Genética , Mastectomia/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mama/imunologia , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
10.
Oncologist ; 21(11): 1298-1305, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27742906

RESUMO

BACKGROUND: Evidence on the management and treatment of male breast cancer is scant. We report the analysis of a multicenter Italian series of patients with male breast cancer treated with eribulin. To our knowledge, this is the first report on the use or eribulin in this setting. PATIENTS AND METHODS: Patients were retrospectively identified in 19 reference centers. All patients received eribulin treatment, according to the standard practice of each center. Data on the identified patients were collected using a standardized form and were then centrally reviewed by two experienced oncologists. RESULTS: A total of 23 patients (median age, 64 years; range, 42-80) were considered. The median age at the time of diagnosis of breast cancer was 57 years (range, 42-74). HER2 status was negative in 14 patients (61%), and 2 patients (9%) had triple-negative disease. The most common metastatic sites were the lung (n = 14; 61%) and bone (n = 13; 56%). Eribulin was administered for a median of 6 cycles (range, 3-15). All patients reported at least stable disease; two complete responses (9%) were documented. Eribulin was well-tolerated, with only four patients (17%) reporting grade 3 adverse events and two (9%) with treatment interruptions because of toxicity. Eight subjects (35%) did not report any adverse event during treatment. For patients with a reported fatal event, the median overall survival from the diagnosis of metastatic disease was 65 months (range, 22-228). CONCLUSION: Although hampered by all the limitations of any retrospective case series, the results of the present study suggest, for the first time, the use of eribulin as therapy for male breast cancer. IMPLICATIONS FOR PRACTICE: Evidence on the management and treatment of male breast cancer is eagerly awaited. Although hampered by all the limitations of any retrospective case series, the results of the present study suggest, for the first time, the use of eribulin as therapy for male breast cancer.

11.
Future Oncol ; 12(3): 281-4, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26775918

RESUMO

International Liver Cancer Association Congress 2015, Paris, France, 4-6 September 2015 Since its creation 9 years ago, in 2007, the International Liver Cancer Association has focused on the multidisciplinary approach to liver cancer due to advances in hepatology science and care worldwide. In its 2015 annual conference, held on 4-6 September in Paris, France, the most recent progresses in the basic biology, management and treatment of liver cancer have been presented. This report, divided into two parts, introduces and critically reviews some of the most intriguing topics discussed at the meeting.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Gerenciamento Clínico , Humanos
12.
Future Oncol ; 12(3): 285-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26776157

RESUMO

International Liver Cancer Association Congress 2015, Paris, France, 4-6 September 2015 Since its creation 9 years ago, in 2007, the International Liver Cancer Association has focused on the multidisciplinary approach to liver cancer due to advances in hepatology science and care worldwide. In its 2015 annual conference, held on 4-6 September in Paris, France, the most recent progresses in the basic biology, management and treatment of liver cancer have been presented. This report, divided into two parts, introduces and critically reviews some of the most intriguing topics discussed at the meeting.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Gerenciamento Clínico , Humanos
14.
Transl Oncol ; 8(4): 273-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26310373

RESUMO

Although several molecular markers have been proposed as prognostic of disease progression in Hepatocellular carcinoma (HCC), predictive markers of response to treatment are still unsatisfactory. Here, we propose a genetic polymorphism as a potential predictive factor of poor prognosis in HCC patients treated with transcatheter arterial chemoembolization (TACE). In particular, we show that the guanosine insertion/deletion polymorphism in the promoter region of SERPINE1 gene at the -675 bp position, named 4G/4G, predicts poor prognosis in a cohort of 75 patients with HCC undergoing TACE. By a combination of ELISA and SERPINE1 promoter study, we found that the presence of elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) in patients with 4G/4G genotype is significantly associated with reduced overall survival compared to patients with 5G/5G or 4G/5G genotype in HCC patients after TACE. Our analysis provided evidence that variation in SERPINE1 gene plays a role in defining the outcome in patients treated with TACE. In addition to a poor disease outcome, the 4G/4G variant represents an unfavorable predictive factor for response to chemotherapy as well.

15.
Future Oncol ; 11(13): 1863-80, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26161924

RESUMO

Sorafenib is an oral multikinase inhibitor with anticancer activity against a wide spectrum of cancers. It is currently approved for the treatment of patients with hepatocellular carcinoma, advanced renal cell carcinoma or progressive, locally advanced or metastatic differentiated thyroid carcinoma. In this review, we present a number of studies that investigated the efficacy and safety of sorafenib in these settings. We also discuss the perspectives on the use of this molecule, including the role of sorafenib as comparator for the development of new drugs, the combination of sorafenib with additional therapies (such as transarterial chemoembolization for hepatocellular carcinoma) and the use of this treatment in several other advanced refractory solid tumors.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Sorafenibe
17.
Oncol Lett ; 8(4): 1783-1787, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25202410

RESUMO

The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55-73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2-6.2) and 10.4 (95% CI, 10-11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC.

18.
Cancer Causes Control ; 25(11): 1531-41, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25135616

RESUMO

PURPOSE: Colon carcinoma is a malignant tumor showing a marked preference to metastasize to distant organs. The presence of circulating tumor cells (CTCs) in the peripheral blood is a prerequisite for the formation of distant metastases. However, whether circulating cytokines are linked to the circulation of tumor cells, as individual cells or clusters, remain unclear. In this study, we investigated the circulating levels of TGF-beta, CXCL1, VEGF and PAI-1 as potential bioindicators of the presence of CTCs in patients with metastatic colon cancer. METHODS: Circulating tumor cells (CTCs) were isolated from peripheral blood by immunomagnetic separation and phenotypically characterized in a cohort of 103 patients with metastatic colon cancer. TGF-beta, CXCL1, VEGF and PAI-1 concentrations were determined by immunoassay in plasma samples from the same patients. RESULTS: We detected two different populations of CTCs, single cells or clusters in patients with metastatic colon cancer. Importantly, we found that the presence of clustered CTCs is significantly associated with elevated circulating levels of TGF-beta and CXCL1 and with reduced overall survival. Finally, we observed that circulating levels of cytokines are differently associated with the two populations of CTCs. CONCLUSIONS: Taken together, these findings show that detection of clustered CTCs represents a negative prognostic factor in patients with metastatic colon cancer. The presence of clustered CTCs is associated with elevated circulating levels of cytokines such as TGF-beta and CXCL1. This suggests an additional role for circulating cytokines as predictive tool for cancer prognosis and diagnosis of minimal residual disease as well as assessment of tumor sensitivity to anticancer therapy.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/mortalidade , Predisposição Genética para Doença , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiocina CXCL1/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Citocinas/sangue , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Fenótipo , Prognóstico , Fator de Crescimento Transformador beta/sangue
19.
Future Oncol ; 10(7): 1129-32, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24947253

RESUMO

EASL HCC Summit, Geneva, Switzerland, 13-16 February 2014. The European Association for the Study of the Liver (EASL) organized the 2014 EASL HCC Summit in Geneva, Switzerland. We discuss here the most interesting and provocative contents from the clinical program of the summit. The objective of this segment was to provide an in-depth review on the different management issues related to early detection, diagnosis and treatment of hepatocellular carcinoma, and, in addition, to highlight the ways of dealing with such an important and rapidly involving field.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/patologia , Detecção Precoce de Câncer/métodos , Humanos , Neoplasias Hepáticas/patologia
20.
Expert Rev Anticancer Ther ; 14(7): 831-45, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24850249

RESUMO

Transarterial chemoembolization (TACE) is considered as the standard therapy for patients with intermediate-stage hepatocellular carcinoma. However, given the high heterogeneity of this population, no common strategy or protocol standardization has been defined yet. In the last few years TACE treatment has been combined with sorafenib systemic therapy, reporting overall positive results both in terms of safety and efficacy. This systematic review presents and critically discusses the evidence available on the use of TACE in combination (concomitant or sequential) with sorafenib, focusing also on clinical trials currently ongoing to better define an optimal therapeutic strategy for this group of patients.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Ensaios Clínicos como Assunto , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Sorafenibe
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