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1.
Target Oncol ; 16(6): 789-799, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34755244

RESUMO

BACKGROUND: Real-world data on extended follow-up of patients with BRAF V600-mutant metastatic melanoma are limited. We investigated dabrafenib plus trametinib (dab + tram) outside of a clinical trial setting (Individual Patient Program; DESCRIBE Italy). OBJECTIVE: To describe the baseline features, treatment patterns, efficacy, and safety outcomes in patients with BRAF V600-mutant unresectable or metastatic melanoma who had received dab + tram as part of the Managed Access Program (MAP) in Italy. PATIENTS AND METHODS: An observational, retrospective chart review was conducted in Italian patients with BRAF V600-mutant unresectable stage III/IV melanoma receiving dab + tram as part of the MAP. Baseline features, treatment patterns, efficacy, and safety outcomes were evaluated. RESULTS: Overall, 499 patients were included in this analysis. BRAF V600E mutation was seen in 81.4% of patients. Overall response rate achieved in 243 of the 390 evaluable patients was 62.3% (95% CI 57.5-67.1). Median progression-free survival (PFS) was 9.3 months (95% CI 8.6-10.6). Subgroup analyses revealed that patients with normal lactate dehydrogenase (LDH) and ≤ three metastatic sites without brain metastases at baseline had better outcomes. With normal LDH at baseline, median PFS for patients with one or two metastatic sites other than cerebral was 18 months. No new safety signals were observed. Treatment was permanently discontinued because of treatment-emergent adverse events (TEAEs) in 9.2% of patients, and pyrexia (27.3%) was the most common TEAE, with a lower incidence than that in the phase 3 studies of dab + tram. CONCLUSION: Treatment of BRAF V600E-mutant metastatic melanoma with dab + tram in the real-world setting was effective and safe, including the unselected population with several patients having a high tumor burden - concordant with the results of the pivotal phase 3 studies of dab + tram.

2.
Diagnostics (Basel) ; 11(6)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071518

RESUMO

Baseline clinical prognostic factors for recurrent and/or metastatic (RM) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy are lacking. CT-based radiomics may provide additional prognostic information. A total of 85 patients with RM-HNSCC were enrolled for this study. For each tumor, radiomic features were extracted from the segmentation of the largest tumor mass. A pipeline including different feature selection steps was used to train a radiomic signature prognostic for 10-month overall survival (OS). Features were selected based on their stability to geometrical transformation of the segmentation (intraclass correlation coefficient, ICC > 0.75) and their predictive power (area under the curve, AUC > 0.7). The predictive model was developed using the least absolute shrinkage and selection operator (LASSO) in combination with the support vector machine. The model was developed based on the first 68 enrolled patients and tested on the last 17 patients. Classification performance of the radiomic risk was evaluated accuracy and the AUC. The same metrics were computed for some baseline predictors used in clinical practice (volume of largest lesion, total tumor volume, number of tumor lesions, number of affected organs, performance status). The AUC in the test set was 0.67, while accuracy was 0.82. The performance of the radiomic score was higher than the one obtainable with the clinical variables (largest lesion volume: accuracy 0.59, AUC = 0.55; number of tumoral lesions: accuracy 0.71, AUC 0.36; number of affected organs: accuracy 0.47; AUC 0.42; total tumor volume: accuracy 0.59, AUC 0.53; performance status: accuracy 0.41, AUC = 0.47). Radiomics may provide additional baseline prognostic value compared to the variables used in clinical practice.

3.
Int J Surg Case Rep ; 77S: S37-S39, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32891587

RESUMO

INTRODUCTION: Melanoma is one of the most aggressive and one of the fastest growing types of cancer. The occurrence of a malignant melanoma in the gastrointestinal tract, either primary or metastatic, is a rare event. Metastatis from cutaneous malignant melanoma to the gallbladder are a highly uncommon finding, usually associated with diffuse metastatic disease and observed during autopsy. The event of a solitary metastasis of malignant melanoma to gallbladder is barely reported. CASE REPORT: We report a case of a 35-year old Caucasian woman with isolated metastasis of gallbladder from cutaneous primary malignant melanoma managed with laparoscopic cholecystectomy. DISCUSSION: Gallbladder metastasis as a first site of recurrence represents a rare condition for all cancers. Since the occurrence of an isolated gallbladder metastasis of cutaneous melanoma is an uncommon circumstance, no therapeutic guidelines have yet been proposed. Nevertheless cholecystectomy appears to be the standard of care for the treatment of this unusual condition, especially when symptomatic and for palliative purpose. The surgical approach is still debated, with no unanimous consent between mini-invasive surgery and open technique. CONCLUSION: In our case, we decided to carry out a three-port laparoscopic cholecystectomy, preferring a mini-invasive approach considering the good performance status of our patient and her young age.

4.
Oncology ; 98(7): 445-451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348984

RESUMO

BACKGROUND: Target therapy can cause various cardiovascular complications. The aim of this study was to evaluate the burden of cardiovascular complications related to treatment with anti-BCR-ABL tyrosine kinase inhibitors (TKIs) and to determine if there are differences between the latest- and first-generation TKIs. METHODS: A retrospective observational study was carried out on 55 patients (39 men, 16 women; mean age ± SD: 58 ± 11 years) treated with TKIs targeting Bcr-Abl for a median period of 3.5 years. Patients were divided in two groups according to the type of treatment. Group A included patients treated with latest-generation TKI (nilotinib, dasatinib, and ponatinib), while group B included patients treated with first-generation TKI (imatinib). Cardiological evaluation included electrocardiogram, echocardiogram with global longitudinal strain of left ventricle (GLS), and carotid ultrasound scan with arterial stiffness measurement (pulse wave velocity, PWV). Adverse cardiovascular events were recorded in both groups. RESULTS: Statistical analysis showed that cardiovascular adverse events (myocardial ischemia, peripheral artery disease, deep vein thrombosis, and pleural effusion) were significantly more frequent in group A than group B (p value = 0.044). Moreover, there was a significant reduction in GLS and PWV in group A when compared to group B (respectively, p = 0.03 and p = 0.004). CONCLUSIONS: Our study confirms that imatinib is a relatively safe drug, while it reveals that the latest-generation TKIs may cause a burden of cardiovascular complications. GLS and PWV allow detection of early signs of cardiac and vascular toxicity in oncohematologic patients treated with TKI, and their use is advisable.


Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Doença da Artéria Coronariana/induzido quimicamente , Dasatinibe/efeitos adversos , Dasatinibe/uso terapêutico , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Humanos , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Piridazinas/efeitos adversos , Piridazinas/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
5.
Ther Adv Med Oncol ; 11: 1758835919848872, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205506

RESUMO

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients' overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis.

6.
Pharmacol Ther ; 192: 65-73, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29964124

RESUMO

Many new drugs have appeared in last years in the oncological treatment scenario. Each drug carries an important set of adverse events, not less, cardiovascular adverse events. This aspect is even more important considering the increasing use of combination therapies with two drugs, or three drugs as in some ongoing clinical trials. Besides it represents a growing problem for Cardiologists, that face it in every day clinical practice and that will face it probably more and more in the coming years. This work reviews the mechanism of action of BRAF-inhibitors and MEK-inhibitors used together, the pathophysiological mechanisms that lead to cardiovascular toxicity. Particularly, it focuses on hypertension and ejection fraction reduction development. Then, it follows the examination of published data for each combination therapy. A Literature research was carried out using Pubmed selecting review articles, original studies and clinical trials, but mainly focusing on phase 3 studies. This work aims to summarize the knowledge about BRAF-inhibitor and MEK-inhibitor treatment and its cardiovascular toxicity to make it usable and give the basic tools to Cardiologists and Oncologists for a better management of cancer patient undergoing this treatment. Besides a deeper knowledge of the cardiovascular adverse events linked to this treatment and the magnitude of their expression and frequency can lead to a targeted cardiological treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Sistema Cardiovascular/efeitos dos fármacos , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Cardiotoxicidade , Ensaios Clínicos como Assunto , Humanos , Melanoma/tratamento farmacológico , Melanoma/enzimologia
7.
Cancer Immunol Res ; 5(5): 397-407, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28351891

RESUMO

The identification of reciprocal interactions between tumor-infiltrating immune cells and the microenviroment may help us understand mechanisms of tumor growth inhibition or progression. We have assessed the frequencies of tumor-infiltrating and circulating γδ T cells and regulatory T cells (Treg) from 47 patients with squamous cell carcinoma (SCC), to determine if they correlated with progression or survival. Vδ1 T cells infiltrated SSC tissue to a greater extent than normal skin, but SCC patients and healthy subjects had similar amounts circulating. However, Vδ2 T cells were present at higher frequencies in circulation than in the tissue of either cancer patients or healthy donors. Tregs were decreased in the peripheral blood of SCC patients, but were significantly increased in the tumor compartment of these patients. Tumor-infiltrating γδ T cells preferentially showed an effector memory phenotype and made either IL17 or IFNγ depending on the tumor stage, whereas circulating γδ T cells of SCC patients preferentially made IFNγ. Different cell types in the tumor microenvironment produced chemokines that could recruit circulating γδ T cells to the tumor site and other cytokines that could reprogram γδ T cells to produce IL17. These findings suggest the possibility that γδ T cells in SCC are recruited from the periphery and their features are then affected by the tumor microenvironment. Elevated frequencies of infiltrating Vδ2 T cells and Tregs differently correlated with early and advanced tumor stages, respectively. Our results provide insights into the functions of tumor-infiltrating γδ T cells and define potential tools for tumor immunotherapy. Cancer Immunol Res; 5(5); 397-407. ©2017 AACR.


Assuntos
Carcinoma de Células Escamosas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Cutâneas/imunologia , Subpopulações de Linfócitos T/imunologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Citocinas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Cutâneas/patologia , Microambiente Tumoral
8.
Int J Surg Case Rep ; 30: 89-92, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28006719

RESUMO

INTRODUCTION: Male breast cancer (MBC) is a rare disease that accounts for <1% of breast cancer cases. The most common treatment is modified radical mastectomy (MRM). Recently, breast conservative surgery (BCS) is getting popular for MBC treatment. We report a case and reviewed the literature to investigate whether emerging BCS can be considered as an alternative of a more radical surgery. PRESENTATION OF CASE: A 46 y.o. patient, presented with a painless left breast lump over a period of six months. The patient underwent a quadrantectomy at another institution. Pathology revealed an intraductal carcinoma in close proximity to the margins of excision. Adjuvant hormonal therapy was proposed to the patient, who refused and was referred to our Institution. We performed a MRM and a sentinel lymph node biopsy (SLNB). A contralateral breast liposuction and an adenectomy were also performed. The patient underwent also a nipple-areolar complex reconstruction. The patient didn't receive adjuvant therapy. DISCUSSION: Both oncological safety and satisfactory cosmetic outcomes are the goals of MBC treatment. No specific guidelines for MBC treatment have been proposed. MRM is currently the surgical gold standard of MBC (approximately 70% of all cases). Some authors reported that male BCS associated with radiation therapy is a feasible alternative MRM. Taking into account data from the literature and considering the previous surgery, in the case we report, we offered a MRM, SLNB and a contralateral breast symmetrization. CONCLUSION: MRM with SLNB and reconstruction of male breast asymmetry should be still considered as the treatment of choice of MBC.

9.
Tumour Biol ; 37(6): 7109-18, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27043958

RESUMO

Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long- and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models. However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes.


Assuntos
Restrição Calórica , Dieta , Neoplasias/dietoterapia , Neoplasias/prevenção & controle , Animais , Humanos
10.
Cancer Biol Ther ; 17(1): 83-90, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26650572

RESUMO

Germline CDKN2A mutations have been described in 25% to 40% of melanoma families from several countries. Sicilian population is genetically different from the people of Europe and Northern Italy because of its historical background, therefore familial melanoma could be due to genes different from high-penetrance CDKN2A gene. Four hundred patients with cutaneous melanoma were observed in a 6-years period at the Plastic Surgery Unit of the University of Palermo. Forty-eight patients have met the criteria of the Italian Society of Human Genetics (SIGU) for the diagnosis of familial melanoma and were screened for CDKN2A and CDK4 mutations. Mutation testing revealed that none of the families carried mutations in CDK4 and only one patient harboured the rare CDKN2A p.R87W mutation. Unlike other studies, we have not found high mutation rate of CDKN2A in patients affected by familial melanoma or multiple melanoma. This difference could be attributed to different factors, including the genetic heterogeneity of the Sicilian population. It is likely that, as in the Australian people, the inheritance of familial melanoma in this island of the Mediterranean Sea is due to intermediate/low-penetrance susceptibility genes, which, together with environmental factors (as latitude and sun exposure), could determine the occurrence of melanoma.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa/genética , Melanoma/genética , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Itália , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Mutação , Sicília , Transdução de Sinais , Proteína Supressora de Tumor p14ARF/genética
11.
J Plast Reconstr Aesthet Surg ; 68(7): 883-94, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25971418

RESUMO

BACKGROUND: External ear melanoma accounts for only 1% of all cutaneous melanomas, and data on its optimal management and prognosis are limited. AIM: We aim to review the literature on external ear melanoma to guide surgeons in the treatment of this uncommon and peculiar pathology. MATERIALS AND METHODS: A systematic review of English language studies on ear melanoma published from 1993 to 2013 was performed using the PubMed electronic database. Data on epidemiology, oncological treatment (tumor resection and regional lymph nodes management), and reconstruction were extrapolated from selected papers. RESULTS: The total number of patients was 858 (30 studies). The helix was the most common location (57%); superficial spreading melanoma was the most common histopathological subtype (41%). The mean Breslow thickness was 2.01 mm, with 88% of stage I-II patients. Sentinel lymph node biopsy was performed in 45% of patients, with 8% of positive nodes. Available data on its prognosis are fragmentary and contrasting, but the Breslow thickness appears to be the main prognostic factor. There is a tendency towards reduced resection margins and preservation of the underlying perichondrium and cartilage. Local flaps are the most popular reconstructive option. CONCLUSION: To the best of our knowledge, this systematic review presents the largest data series on external ear melanoma. There is no general agreement on its surgical management, but a favorable prognosis seems to justify the tendency towards conservative treatments.


Assuntos
Neoplasias da Orelha/cirurgia , Orelha Externa/cirurgia , Melanoma/secundário , Melanoma/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Neoplasias Cutâneas/cirurgia , Neoplasias da Orelha/patologia , Humanos , Metástase Linfática , Melanoma/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Biópsia de Linfonodo Sentinela , Retalhos Cirúrgicos
12.
J Transl Med ; 12: 116, 2014 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-24885479

RESUMO

BACKGROUND: Ipilimumab improves survival in patients with advanced melanoma. The activity and safety of ipilimumab outside of a clinical trial was assessed in an expanded access programme (EAP). METHODS: Ipilimumab was available upon physician request for patients aged 16 or over with pretreated stage III (unresectable)/IV melanoma, for whom no other therapeutic option was available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Patients with stable disease or an objective response to ipilimumab were eligible for retreatment upon disease progression. Tumour assessments were conducted at baseline and week 12. Patients were monitored for adverse events (AEs) within 3 to 4 days of each scheduled visit. RESULTS: Of 855 patients participating in the EAP in Italy, 833 were evaluable for response. Of these, 13% had an objective immune response, and the immune-related disease control rate was 34%. Median progression-free survival and overall survival were 3.7 and 7.2 months, respectively. Efficacy was independent of BRAF and NRAS mutational status. Overall, 33% of patients reported an immune-related AE (irAE). The frequency of irAEs was not associated with response to ipilimumab. CONCLUSIONS: Outside of a clinical trial setting, ipilimumab is a feasible treatment option in patients with pretreated metastatic melanoma, regardless of BRAF and NRAS mutational status. Data from this large cohort of patients support clinical trial evidence that ipilimumab can induce durable disease control and long-term survival in patients who have failed to respond to prior treatment.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Melanoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Ipilimumab , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
13.
J Exp Clin Cancer Res ; 33: 30, 2014 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-24708900

RESUMO

BACKGROUND: Elderly patients with metastatic melanoma have different disease characteristics and a poorer prognosis than younger patients. Data from clinical trials and expanded access programmes (EAPs) suggest ipilimumab confers a consistent survival benefit and has a similar safety profile across different age groups of patients with metastatic melanoma. Here we report the efficacy and safety of ipilimumab 3 mg/kg in elderly patients enrolled in an EAP in Italy. METHODS: Patients aged > 70 years with pretreated melanoma received ipilimumab 3 mg/kg every 3 weeks for four doses through an EAP. Tumour response was evaluated at baseline and after completion of induction therapy using immune-related response criteria and patients were monitored throughout the treatment period for adverse events (AEs), including immune-related AEs. RESULTS: The immune-related disease control rate among 188 evaluable patients was 38%, including four patients with an immune-related complete response, 24 with an immune-related partial response and 44 with immune-related stable disease. Median progression-free survival (PFS) was 4.0 months and the 1- and 2-year PFS rates were 21% and 12%, respectively. Median overall survival (OS) was 8.9 months; 1- and 2-year OS rates were 38% and 22%, respectively. The safety profile of ipilimumab was consistent with that observed in the general population of the Italian EAP and treatment-related AEs generally resolved within a median of 2 weeks with treatment as per protocol-specific guidelines. CONCLUSIONS: These results suggest ipilimumab is a feasible treatment option in elderly patients with metastatic melanoma. Ipilimumab treatment was generally well tolerated and resulted in clinical benefit and extended survival in elderly patients treated at centres in Italy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Melanoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Feminino , Humanos , Ipilimumab , Itália , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
14.
Cancer Immunol Immunother ; 63(7): 675-83, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24695951

RESUMO

BACKGROUND: Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research. PATIENTS AND METHODS: Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12. RESULTS: Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12). CONCLUSION: Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/imunologia , Melanoma/tratamento farmacológico , Melanoma/imunologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Oculares/patologia , Feminino , Humanos , Ipilimumab , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
15.
Cancer Biol Ther ; 15(6): 678-82, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24618694

RESUMO

Androgen-deprivation therapy (ADT) has been reported to be active in androgen receptor (AR)-expressing, relapsed/metastatic (RM), salivary gland cancers (SGCs). Abiraterone, an inhibitor of androgen synthesis, has recently been approved as a second-line treatment in hormone-resistant (HR) prostate cancer (PCa) patients. Two patients with AR-positive HR-RM adenocarcinoma, NOS of the salivary glands have been treated with abiraterone. This is the first time that this agent has been reported to be active in tumors other than HRPCa. Immunohistochemical analysis showed overexpression of EGFR, HER2, and HER3 in both untreated primary tumors. Sequencing analysis revealed a TP53 non-functional mutation in one case and a PIK3CA-activating mutation in the other. In conclusion, second line activity of ADT in AR-expressing, adenocarcinoma, NOS of salivary glands further strengthens the pathogenic and therapeutic role of AR signaling in AR-positive SGCs.


Assuntos
Adenocarcinoma/tratamento farmacológico , Androstenóis/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Receptores Androgênicos/metabolismo , Neoplasias das Glândulas Salivares/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Adulto , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Androstenos , Anilidas/farmacologia , Anilidas/uso terapêutico , Antineoplásicos Hormonais/farmacologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/patologia , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Compostos de Tosil/farmacologia , Compostos de Tosil/uso terapêutico , Resultado do Tratamento , Pamoato de Triptorrelina/farmacologia , Pamoato de Triptorrelina/uso terapêutico
16.
J Chemother ; 26(4): 193-201, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24621162

RESUMO

The degree to which interferon (IFN) alpha-2b offers real clinical benefits in the adjuvant therapy of melanoma at high risk of recurrence is a subject of debate. This, together with questions over optimal treatment scheme and concerns over toxicity, has limited its clinical use. On the basis of a review of the literature, an Italian Expert Panel has made practical recommendations for a consistent approach in the use of IFN. Although it is clear that more research into predictive factors to identify patients most likely to benefit from adjuvant IFN therapy is required, IFN remains the only currently available adjuvant option for melanoma. Based on meta-analyses of clinical trials, there is clear evidence that treatment with IFN is beneficial with regard to overall and recurrence-free survival (RFS). As such, IFN should be offered to patients who are at high risk of recurrence. Specific recommendations with regard to disease stage are provided.


Assuntos
Interferon-alfa/uso terapêutico , Melanoma/tratamento farmacológico , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Humanos
17.
Cancer Invest ; 32(4): 144-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24484235

RESUMO

Of 93 patients with pretreated, BRAF(V600) mutation-positive advanced melanoma who received vemurafenib or dabrafenib before (n = 45) or after (n = 48) treatment with ipilimumab 3 mg/kg, median overall survival (mOS) from first treatment was 9.9 and 14.5 months, respectively. Among patients treated with a BRAF inhibitor first, mOS from the end of BRAF inhibition was 1.2 months for those who did not complete ipilimumab treatment as per protocol, compared with 12.7 months for those who did (p < .001). Prospective, randomized studies are required to determine the optimal sequencing of ipilimumab and BRAF inhibitors in patients with BRAF-mutated metastatic melanoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Imidazóis/administração & dosagem , Indóis/administração & dosagem , Ipilimumab , Itália , Estimativa de Kaplan-Meier , Masculino , Melanoma/enzimologia , Melanoma/genética , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Mutação , Oximas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Estudos Retrospectivos , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Sulfonamidas/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Vemurafenib , Adulto Jovem
18.
Eur J Cancer ; 50(1): 121-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24100024

RESUMO

BACKGROUND: Mucosal melanoma is an extremely rare and aggressive malignancy that often remains undetected until it reaches an advanced stage, when effective treatment options are limited. The activity and safety of ipilimumab were assessed in an Expanded Access Programme (EAP) that included patients with metastatic, mucosal melanoma. METHODS: Ipilimumab was available upon physician request for patients aged ⩾16years with stage III (unresectable) or IV skin, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3mg/kg every 3weeks for four doses. Patients with stable disease or an objective response to ipilimumab were eligible for retreatment upon disease progression. Tumour assessments were conducted at baseline and week 12 using immune-related response criteria. Patients were monitored for adverse events (AEs), including immune-related AEs, within 3 to 4days of each scheduled visit. RESULTS: Of 855 patients participating in the EAP in Italy, 71 (8%) had metastatic, mucosal melanoma. With a median follow-up of 21.8months, the response rate was 12% and the immune-related disease control rate was 36%. Median progression-free survival and overall survival were 4.3 and 6.4months, respectively. In total, 34% of patients reported treatment-related AEs of any grade, which were grade 3 or 4 in 9% of patients. AEs were generally manageable as per protocol-specific guidelines. CONCLUSION/INTERPRETATION: Ipilimumab may be a feasible treatment option in pretreated patients with metastatic mucosal melanoma, and warrants further investigation in prospective clinical trials.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Melanoma/tratamento farmacológico , Membrana Mucosa/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Ipilimumab , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento , Adulto Jovem
19.
PLoS One ; 7(11): e49878, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23189169

RESUMO

T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that γδ T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating γδ T cells from 74 patients with primary melanoma. We found that γδ T cells represent the major lymphocyte population infiltrating melanoma, and both Vδ1(+) and Vδ2(+) cells are involved. The majority of melanoma-infiltrating γδ cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal γδ T cell lines obtained from tumor-infiltrating immune cells produced IFN-γ and TNF-α and were capable of killing melanoma cell lines in vitro. The cytotoxic capability of Vδ2 cell lines was further improved by pre-treatment of tumor target cells with zoledronate. Moreover, higher rate of γδ T cells isolation and percentages of Vδ2 cells correlate with early stage of development of melanoma and absence of metastasis. Altogether, our results suggest that a natural immune response mediated by γδ T lymphocytes may contribute to the immunosurveillance of melanoma.


Assuntos
Linfócitos do Interstício Tumoral/imunologia , Melanoma/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Citocinas/biossíntese , Citotoxicidade Imunológica , Feminino , Humanos , Memória Imunológica , Imunofenotipagem , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T/metabolismo
20.
J Cell Physiol ; 221(2): 343-9, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19585492

RESUMO

It is essential to reach a better understanding of "flat epithelial atypia/columnar cell lesions" (FEA/CCLs) in breast core biopsies. Our aim was to explore their biological nature, in order to predict the likelihood of an upgrade to carcinoma. "Cytological grading" has been specially focused, in view of its possible utility in the choice of management. One hundred thirty of a total of 900 cases core needle (CN)/vacuum-assisted biopsies (VABs), with diagnoses of "hyperplasia" and "atypia" were retrospectively re-evaluated. Pathological findings of further excision biopsies (FEBs) performed in 40/75 patients with follow-up were compared with the previous diagnoses. In all cases, both Ki-67 and c-kit immunoreactivities were explored and compared with both normal breast tissues and subsequently documented cancers, with special reference to the hyperplastic FEA/CCLs, with "mild" atypia (FEA/CCHAm). Sixteen cases were re-diagnosed as "usual ductal hyperplasia" (UDH), 60 as "columnar cell hyperplasia" (CCH), and 54 as FEA/CCHA, 30 of which FEA/CCHAm and 24 FEA/CCHAh (with high atypia). Significantly, the Ki-67 index proved to be on the increase and c-kit expression on the decrease in FEA/CCHA lesions, mainly in the FEA/CCHAh group and in the subsequently observed cancers, compared with either benign tissues or the FEA/CCH cases. It was also significant that most of the carcinomas were found in FEBs within the FEA/CCHAh group. In this study cytological grading, together with Ki-67 and c-kit indices, proved to be helpful in FEA/CCLs evaluation. With regard to FEA/CCHAm lesions, an adequate surveillance appears to be a more appropriate management tool than FEB, as a result of their biological nature and behavior.


Assuntos
Mama/patologia , Células Epiteliais/patologia , Imuno-Histoquímica/métodos , Antígeno Ki-67/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Adulto , Idoso , Anticorpos Monoclonais/imunologia , Biópsia , Feminino , Humanos , Pessoa de Meia-Idade
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