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1.
Cancers (Basel) ; 16(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38791882

RESUMO

Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR, and ALK wild-type tumors. However, given the differences between patients treated in routine clinical practice and those treated in a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-ups, we designed an observational retrospective study of patients with metastatic NSCLC who were treated with pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were PFS and OS, determined using the Kaplan-Meier method. Response and safety were also evaluated. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression, and habitual smoking were prognostic factors for PFS, while age, sex, ECOG PS, habitual smoking and histology had an impact on OS. Multivariable analysis confirms the prognostic role of PD-L1 for PFS and of ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of pembrolizumab in the first-line setting, as well as a safety profile consistent with the results of Keynote-024. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

2.
Front Oncol ; 14: 1351995, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601759

RESUMO

Introduction: The phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known EGFR and ALK driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 <50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program. Methods: PEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan-Meier method), response to therapy, and tolerability. Results: Until February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5-9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate. Conclusion: The results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily.

3.
Arch Pharm (Weinheim) ; 356(10): e2300354, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37603378

RESUMO

Targeting tubulin polymerization and depolymerization represents a promising approach to treat solid tumors. In this study, we investigated the molecular mechanisms underlying the anticancer effects of a structurally novel tubulin inhibitor, [4-(4-aminophenyl)-1-(4-fluorophenyl)-1H-pyrrol-3-yl](3,4,5-trimethoxyphenyl)methanone (ARDAP), in two- and three-dimensional MCF-7 breast cancer models. At sub-cytotoxic concentrations, ARDAP showed a marked decrease in cell proliferation, colony formation, and ATP intracellular content in MCF-7 cells, by acting through a cytostatic mechanism. Additionally, drug exposure caused blockage of the epithelial-to-mesenchymal transition (EMT). In 3D cell culture, ARDAP negatively affected tumor spheroid growth, with inhibition of spheroid formation and reduction of ATP concentration levels. Notably, ARDAP exposure promoted the differentiation of MCF-7 cells by inducing: (i) expression decrease of Oct4 and Sox2 stemness markers, both in 2D and 3D models, and (ii) downregulation of the stem cell surface marker CD133 in 2D cell cultures. Interestingly, treated MCF7 cells displayed a major sensitivity to cytotoxic effects of the conventional chemotherapeutic drug doxorubicin. In addition, although exhibiting growth inhibitory effects against breast cancer cells, ARDAP showed insignificant harm to MCF10A healthy cells. Collectively, our results highlight the potential of ARDAP to emerge as a new chemotherapeutic agent or adjuvant compound in chemotherapeutic treatments.


Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Proliferação de Células , Trifosfato de Adenosina , Linhagem Celular Tumoral
4.
Life (Basel) ; 13(5)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37240815

RESUMO

Thymic epithelial tumors (TETs), including thymoma, thymic carcinoma and neuroendocrine tumors, are uncommon tumors that originate from the epithelial cells of the thymus. Nevertheless, despite their rarity, they represent the most common tumor type located in the anterior mediastinum. Therapeutic choices based on staging and histology may include surgery with or without neoadjuvant or adjuvant therapy represented by chemotherapy, radiotherapy or chemo-radiotherapy. For patients with advanced or metastatic TETs, platinum-based chemotherapy remains the standard first-line treatment; however, some new drugs and combinations are currently under evaluation. In any case, proper management of patients with TETs requires a multidisciplinary team approach to personalize care for each patient.

5.
Life (Basel) ; 12(12)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36556468

RESUMO

Lung cancer, of which non-small-cell lung cancer (NSCLC) represents about 80% of all cases, is the second most common cancer diagnosed in the general population and one of the major causes of cancer-related deaths worldwide. Overall, the outcomes of patients with advanced NSCLC are still disappointing despite advances in diagnosis and treatment. In recent years immune-checkpoint inhibitors (ICIs), administered alone or in combination with chemotherapy, have revolutionized the treatment landscape of patients with advanced non-small-cell lung cancer. However, until now, tissue expression of PD-L1 and tumor mutation burden represent the only available biomarkers for NSCLC patients treated with ICIs. A growing body of evidence showed that tumor-derived exosomes (TDEs) have the PD-L1 protein on their surface and that they are involved in angiogenesis, tumor growth, invasion, metastasis and immune escape. This review focused on the potential clinical applications of TDEs in NSCLC, including their possible role as a biomarker for prognosis and disease monitoring in patients undergoing immunotherapy.

6.
Med Oncol ; 39(7): 107, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35553247

RESUMO

Non-metastatic castration-resistant prostate cancer (nmCRPC) indicates a condition characterized by the progression of the prostate-specific antigen without radiographic evidence of distant metastasis on conventional imaging during androgen deprivation therapy (ADT). Recently, 3 phase III trials have shown that the addition of next-generation androgen-receptor inhibitors (ARIs) apalutamide, darolutamide, and enzalutamide to ADT allows patients with high-risk nmCRPC to delay the appearance of metastasis and to obtain long-term clinical benefits. However, the lack of head-to head comparison makes it difficult to choose one among these agents. We reviewed the literature and explained the rationale of the possible therapeutic choices. In any case, the availability of novel ARIs means that patients with nmCRPC have now a new effective treatment option that provides them a renewed hope.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Androgênios , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Resultado do Tratamento
7.
Med Oncol ; 39(5): 56, 2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35150371

RESUMO

Oligoprogression is an emerging concept in oncology representing a state where after an initially successfully local or systemic treatment a disease progression occurs characterized by the appearance of a single or few new lesions. We reviewed the literature and explained the rationale of the therapeutic choices by referring to the current guidelines and literature data. In any case, the treatment of oligometastatic disease should be tailored to suit the individual patient with the aim of maximizing the benefit of each line of therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias Pulmonares/complicações , Carcinoma Pulmonar de Células não Pequenas/terapia , Progressão da Doença , Humanos , Neoplasias Pulmonares/terapia , Metástase Neoplásica , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
J Thorac Dis ; 12(7): 3815-3820, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32802463

RESUMO

Poor survival of lung cancer (LC) patients depends on several factors first of all the delay in the diagnosis, considering that the majority of patients have an advanced-stage disease at the time of diagnosis. In this context, use of screening to increase the percentage of early LC detection can play a crucial role. After the preliminary unsatisfactory experiences with chest X-rays and sputum cytology, low dose computed tomography (LDCT) has become the best method for LC screening. In particular, several randomized LDCT screening trials conducted in the last year showed significant reductions in LC mortality in high-risk subjects. This review focuses on both recent advances in LC screening and some open questions.

9.
J Thorac Dis ; 12(7): 3866-3876, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32802468

RESUMO

Smoking increases mortality from all causes and has a crucial role in atherosclerotic cardiovascular disease (ASCVD). Active smoking and secondhand smoke exposure determine more than 30% of coronary heart disease (CHD) mortality. The exact mechanisms of cardiovascular damages are not well known, but the detrimental effect of smoking on endothelial function has long been recognized. Smoking elicits oxidative processes, negatively affects platelet function, fibrinolysis, inflammation and vasomotor function; all these proatherogenic effects double the 10-year risk of fatal events in smokers compared to non smokers. An intriguing issue about smoking is the vulnerability of female gender. The mortality from cardiovascular diseases (CVDs) is higher in female than male smokers and female smokers show a 25% higher risk of developing CHD than men with the same exposure to tobacco smoke. This female vulnerability seems to be related to genes involved in thrombin signaling. The effects of smoking cessation have also been extensively studied. Cessation at an early age (40 years) has an impressive 90% reduction in the excess risk of death. In this review we report recent data about the causal link between smoking and CVDs and about the benefits of smoking cessation.

10.
Med Oncol ; 37(9): 80, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32767203

RESUMO

Cancer patients are at particular risk from COVID-19 since they usually present multiple risk factors for this infection such as older age, immunosuppressed state, comorbidities (e.g., chronic lung disease, diabetes, cardiovascular diseases), need of frequent hospital admissions and visits. Therefore, in the COVID era, oncologists should carefully weigh risks/benefits when planning cancer therapies and follow-up appointments. Recently, several scientific associations developed specific guidelines or recommendations to help physicians in their clinical practice. This review focuses on main available guidelines/recommendations regarding the cancer patient management during the COVID-19 pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Internacionalidade , Oncologia/normas , Neoplasias/epidemiologia , Pneumonia Viral/epidemiologia , Guias de Prática Clínica como Assunto/normas , COVID-19 , Infecções por Coronavirus/terapia , Humanos , Oncologia/métodos , Neoplasias/terapia , Pandemias , Pneumonia Viral/terapia , SARS-CoV-2
11.
Future Oncol ; 15(20): 2423-2433, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31237152

RESUMO

Aim: At present three immune checkpoint inhibitors (ICIs), two anti-PD-1 (nivolumab and pembrolizumab) and one anti-PD-L1 (atezolizumab) can be used in pretreated non-small-cell lung cancer patients. The aim of this meta-analysis is an indirect comparison between anti-PD-1 and anti-PD-L1 inhibitors. Methods: Seven studies (>4000 patients) were considered. Results: Considering the overall survival ICIs showed very robust efficacy over docetaxel, while in terms of progression-free survival the therapy with ICIs is slightly favored. Anti-PD-1 gives a more significant benefit than anti-PD-L1; however, excluding the KEYNOTE 010 trial that enrolled only PD-L1-positive patients, the subgroup difference remains only in terms of progression-free survival. Conclusion: This meta-analysis confirms the superiority of ICIs over docetaxel in pretreated non-small-cell lung cancer patients and would indicate a slight benefit from anti-PD-1 than from anti-PD-L1 inhibitors, always keeping in mind the possible biases of this indirect comparison.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Intervalo Livre de Progressão , Análise de Sobrevida
12.
Med Oncol ; 35(7): 98, 2018 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-29845408

RESUMO

Malignant pleural mesothelioma (MPM) is a very aggressive malignancy, mainly caused by asbestos exposure. Patients with MPM have a poor prognosis that remained substantially unchanged in the last few years and limited effective therapeutic options with no recognized second or further-line therapy. In this context, also in view of the positive results observed in other tumor types, immunotherapy could play a relevant role. This review focuses on the most promising immunotherapies being investigated in MPM.


Assuntos
Antineoplásicos/uso terapêutico , Imunoterapia , Neoplasias Pulmonares/terapia , Mesotelioma/terapia , Neoplasias Pleurais/terapia , Antígeno CTLA-4/antagonistas & inibidores , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Mesotelioma Maligno , Proteína 2 Ligante de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores
13.
J Thorac Dis ; 9(Suppl 13): S1359-S1363, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29184674

RESUMO

Circulating tumor cells (CTCs) are rare epithelial cells that can be found in the peripheral blood of cancer patients. A growing body of evidence indicates that CTCs may play a role in non-small cell lung cancer (NSCLC) for diagnosis, therapy monitoring and prognostic purposes. CTCs evaluation could be particularly relevant in this clinical setting, considering that physicians often have difficulty in obtaining an adequate tumor tissue and that patients are not always suitable to receive a re-biopsy. In the current review, we will focus on the molecular characterization and prognostic significance of CTCs in NSCLC patients.

14.
Med Oncol ; 34(6): 110, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28456992

RESUMO

Small cell lung cancer (SCLC) is a very aggressive malignancy characterized by high cellular proliferation and early metastatic spread. In fact, although SCLC is a chemosensitive and radiosensitive disease, the initial responsiveness to chemotherapy is usually followed by development of resistance and the prognosis remains poor with a median survival of less than 12 months in patients with extensive disease (ED-SCLC). Furthermore, no significant progress has been made over the last years, with no newly approved drug. For all these reasons, SCLC represents for the oncologists a major challenge and an exciting field of clinical research. In this review, we analyze the most promising advances in development for SCLC with a special focus on antiangiogenic treatments, immunotherapy, novel chemotherapeutic and targeted agents.


Assuntos
Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/terapia , Antineoplásicos , Sistemas de Liberação de Medicamentos , Humanos , Imunoterapia
15.
Lung Cancer ; 107: 59-64, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27339469

RESUMO

Recent experiences indicate that, as already reported for other types of cancer, circulating tumor cells (CTCs) may play a role also in non small cell lung cancer (NSCLC) for diagnosis, therapy monitoring and prognostic purposes. CTCs evaluation could be particularly relevant in this clinical setting not only for the objective difficulty in obtaining tumor tissue, but also because of the lack of reliable tumor markers. In the current review, we will focus on the possible applications of CTCs in NSCLC patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Células Neoplásicas Circulantes/patologia , Quinase do Linfoma Anaplásico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/terapia , Contagem de Células , Tomada de Decisão Clínica , Receptores ErbB/genética , Humanos , Biópsia Líquida , Neoplasias Pulmonares/sangue , Mutação , Células Neoplásicas Circulantes/metabolismo , Prognóstico , Receptores Proteína Tirosina Quinases
17.
Semin Nucl Med ; 46(3): 239-42, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27067504

RESUMO

Chemotherapy represents the cornerstone of treatment for patients with small cell lung cancer (SCLC); however, standard therapy has reached a plateau in improving patient survival with overall disappointing results. The demonstration that SCLC expresses neuroendocrine markers, such as somatostatin (SST) receptors, has led to use SST analogs or radiolabeled SST analogs in the treatment of SCLC patients. In the current review, we would focus on the possible role of SST analogs in SCLC.


Assuntos
Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/terapia , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Animais , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Receptores de Somatostatina/metabolismo , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/radioterapia , Somatostatina/metabolismo
18.
Biologics ; 10: 1-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26858523

RESUMO

Neutropenia and febrile neutropenia (FN) are frequent and potentially fatal toxicities of myelosuppressive anticancer treatments. The introduction of granulocyte colony-stimulating factors (G-CSFs) in clinical practice has remarkably reduced the duration and severity of neutropenia, as well as the incidence of FN, thus allowing the administration of chemotherapeutic agents at the optimal dose and time with lower risk. The current scenario of G-CSFs in Europe includes filgrastim, lenograstim, some G-CSF biosimilars, and pegfilgrastim. Recently, a novel long-acting G-CSF, lipegfilgrastim, became available. Lipegfilgrastim is a glycopegylated G-CSF, alternative to pegfilgrastim, and has shown in randomized trials, to be equivalent to pegfilgrastim in reducing the incidence of severe neutropenia and FN in patients with breast cancer receiving chemotherapy, with a similar safety profile. Furthermore, lipegfilgrastim was more effective than the placebo in reducing the incidence of severe neutropenia, its duration, and time to absolute neutrophil count recovery, in patients with non-small cell lung cancer receiving myelosuppressive therapy. Although the number of studies currently published is still limited, lipegfilgrastim seems to be a promising drug in the management of chemotherapy-induced neutropenia.

19.
Future Oncol ; 11(14): 2043-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26198834

RESUMO

Crizotinib is a multitarget tyrosine kinase inhibitor and it represents the standard of care in patients with anaplastic lymphoma kinase translocated non-small-cell lung cancer. Crizotinib is generally well tolerated and the most frequent adverse events include gastrointestinal effects, visual disorders, edema, fatigue and liver enzyme abnormalities. However, due to the increasing clinical experience with crizotinib, other toxicities are emerging, such as Q-wave T-wave interval prolongation and bradycardia. In the current review we will focus on the management of crizotinib-related cardiotoxicity.


Assuntos
Cardiotoxicidade/terapia , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Quinase do Linfoma Anaplásico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Bradicardia/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/prevenção & controle , Crizotinibe , Interações Medicamentosas , Frequência Cardíaca/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Receptores Proteína Tirosina Quinases/metabolismo
20.
Ther Adv Respir Dis ; 9(5): 242-50, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26016841

RESUMO

The discovery of epidermal growth factor receptor activating mutations (EGFR Mut+) has determined a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). In several phase III studies, patients with NSCLC EGFR Mut+ achieved a significantly better progression-free survival when treated with a first- (gefitinib, erlotinib) or second-generation (afatinib) EGFR tyrosine kinase inhibitor (TKI) compared with standard chemotherapy. However, despite these impressive results, most patients with NSCLC EGFR Mut+ develop acquired resistance to TKIs. This review will discuss both the mechanisms of resistance to TKIs and the therapeutic strategies to overcome resistance, including emerging data on third-generation TKIs.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
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