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1.
Folia Med (Plovdiv) ; 64(2): 354-358, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35851793

RESUMO

Melanoma is the most rapidly increasing cancer in the world. Associated morbidity and mortality are mainly related to metastatic potential. Metastases to the breast from malignant melanoma are rare and represent only 1.3%-2.7% of reported cases. The aim of this study was to present a rare case of metastatic malignant melanoma to the breast. A 51-year-old woman was admitted for management of a palpable mass of the left breast. The past medical history referred to a sizable nodular melanoma that was removed from her back. Classification of the breast lesion was BI-RADS 5. Core needle biopsy was compatible with the diagnosis of malignant melanoma. Immunohistochemical evaluation was positive for Mart1 and Ki67. Subsequent staging was indicative of multiple secondary foci in the liver and bones. The patient was administered a combination of PD L1 inhibitor nivolumab with the anti-CTLA4 inhibitor ipilimumab followed by additional targeted therapy with the BRAF inhibitor vemurafenib. Metastasis to the breast from malignant melanoma is extremely rare. Nevertheless, breast metastases must be suspected in patients with a history of malignant melanoma. Moreover, recent breakthroughs in the Braf and MEK inhibitors and immune checkpoint inhibition therapies have impressively improved prognosis in patients affected by melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Feminino , Humanos , Ipilimumab/uso terapêutico , Melanoma/patologia , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas B-raf , Neoplasias Cutâneas/patologia , Melanoma Maligno Cutâneo
2.
Front Surg ; 9: 1069802, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36704507

RESUMO

Background: Patients with pancreatic cancer (PC), which may involve major peripancreatic vessels, have been generally excluded from surgery, as resection was deemed futile. The purpose of this study was to analyze the results of portomesenteric vein resection in borderline resectable or locally advanced PC. This study comprises the largest series of such patients in Greece. Materials and Methods: Investigator-initiated, retrospective, noncomparative study of patients with borderline resectable or locally advanced adenocarcinoma undergoing pancreatectomy en-block with portal and/or superior mesenteric vein resection in a tertiary referral center in Greece between January 2014 and October 2021. Follow-up was complete up to December 2021. Operative and outcome measures were determined. Results: Forty patients were included. Neoadjuvant therapy was administered to only 58% and was associated with smaller tumor size (median: 2.9 cm vs. 4.2 cm, p = 0.004), but not with increased survival. Though venous wall infiltration was present in 55%, it was not associated with tumor size, or Eastern Cooperative Oncology Group (ECOG) status. Resection was extensive: a median of 27 LNs were retrieved, R0 resection rate (≥1 mm) was 87%, and median length of resected vein segments was 3 cm, requiring interposition grafts in 40% (polytetrafluoroethylene). Median ICU stay was 0 days and length of hospitalization 9 days. Postoperative mortality was 2.5%. Median follow-up was 46 months and median overall survival (OS) was 24 months. Two-, 3- and 5-year OS rates were 49%, 33%, and 22% respectively. All outcomes exceeded benchmark cutoffs. Lower ECOG status was positively correlated with longer survival (ECOG-0: 32 months, ECOG-1: 24 months, ECOG-2: 12 months, p = 0.02). Conclusion: This series of portomesenteric resection in borderline resectable or locally advanced PC demonstrated a median survival of 2 years, extending to 32 months in patients with good performance status, which meet or exceed current outcome benchmarks.

3.
World J Clin Oncol ; 10(4): 183-191, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31114750

RESUMO

BACKGROUND: Desmoid tumors (DT) are locally advanced but histologically benign monoclonal neoplasms that can occur from any musculoaponeurotic structure. The aim of this report is to analyze a rare clinical case of an aggressive intra-abdominal DT successfully treated with sorafenib. CASE SUMMARY: A 36-year-old man presented with increasing colicky abdominal pain and a self-palpable mass in his left abdomen. Fourteen years earlier he was diagnosed with a large intra-abdominal tumor, which adhered to the left colonic flexure, part of the major gastric curvature and the spleen. Subsequent exploratory laparotomy revealed a voluminous mass in the epigastrium, arising from the posterior surface of the stomach and invading the superior mesenteric vessels, transverse mesocolon and the small bowel mesentery. As the tumor was unresectable, a jejunojejunal bypass was performed. Traditional therapeutic interventions proved insufficient, and the patient was started on sorafenib with a subsequent full-disease response. CONCLUSION: DT's pathogenesis has been associated with mutations in the adenomatous polyposis coli (APC) gene or beta-catenin gene CTNNB1, sex steroids or previous surgical trauma. Local treatment modalities, such as surgery or radiotherapy, are implemented in aggressively progressing or symptomatic patients. Sorafenib is a hopeful therapeutic option against DTs, while several pharmacological agents have been successfully used.

4.
Anticancer Res ; 36(4): 1581-90, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27069134

RESUMO

BACKGROUND: Gastric cancer is a relatively common malignancy. Recently, the presence of the human epidermal growth factor receptor 2 (HER2) was identified as a molecular target in a proportion of patients who benefited from the addition of appropriate anti-HER2 treatments. Our study explored the clinical and prognostic role of known HER family members, human epidermal growth factor receptor 1 (EGFR or HER1), HER2, HER3 and HER4. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 249 gastric cancer patients were studied by immunohistochemistry for protein expression of EGFR, HER2, HER3 and HER4. RESULTS: Of the 249 evaluable patients, 32 did not have complete data of treatment details and/or follow-up and were excluded from the survival analyses. Of the 217 patients with complete treatment and follow-up data, 178 were operated and treated for early disease (group 1), while 39 for advanced disease (group 2). The frequency of positive EGFR, HER2, HER3 and HER4 protein expression in all patients was 17.5%, 11.8%, 14.8% and 32.9%, respectively. There were no differences in protein expression of any of the markers between the two groups. There were, however, statistically significant associations between HER4 and all other HER family members, as well as between HER2 and HER3 expression. Of note, EGFR-positive membranous protein expression was significantly associated with the presence of lymphovascular invasion (p=0.027) and HER3 and HER4 negative cytoplasmic protein expression with well/moderately-differentiated tumors (p=0.030 and p=0.014, respectively). None of the HER family members were of prognostic value for OS in univariate analysis. CONCLUSION: The present study confirmed the known protein expression frequencies of HER family members in gastric cancer in a Greek population. Several associations were observed among the HER family members and between clinicopathological characteristics and HER family members. Further research is needed on their exact prognostic role, as well as their therapeutic targeting.


Assuntos
Receptores ErbB/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Grécia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/epidemiologia , Adulto Jovem
5.
Oncology ; 89(1): 53-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25766505

RESUMO

BACKGROUND: The adenocarcinoma subtype of non-small cell lung cancer (adeno-NSCLC) is routinely treated with chemotherapy if patients do not have molecular aberrations such as epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements. There are currently no validated biomarkers that can predict if patients will gain clinical benefit from chemotherapy, leading to a majority of patients receiving many cycles of unnecessary chemotherapy. We hypothesized that the percentage rise in plasma caspase-cleaved cytokeratin 18 (cCK18) and total cytokeratin 18 (tCK18) assessed before and after chemotherapy correlates with the radiological response to chemotherapy. METHODS: Plasma samples from 40 patients with stage IV adeno-NSCLC, treated with first-line chemotherapy with carboplatin (AUC5) plus pemetrexed (500 mg/m(2)), were collected prior to chemotherapy and 48 h after treatment. ELISA was used to quantify cCK18 and tCK18. RESULTS: The male-to-female ratio was 3:1, and the median age of patients was 63 years. Patients who had a clinical benefit (complete response, partial response or stable disease) at the first radiological assessment following chemotherapy had a significantly higher percentage change in plasma tCK18 levels compared to those who had no clinical benefit, i.e. progressive disease (69.5 ± 75.1 vs. 25.3 ± 30.9%, respectively; p = 0.042). The receiver operating characteristic area was 0.712 (p = 0.039). There was an increase in the percentage change in cCK18 in patients with clinical benefit compared to those without clinical benefit but this was not statistically significant (57.6 ± 112.8 vs. 24.38 ± 45.1%, respectively; p = 0.85). CONCLUSIONS: The percentage change in plasma tCK18 levels before and after the first cycle of pemetrexed and carboplatin chemotherapy is associated with clinical benefit. If validated in larger cohorts, this test can be used to identify patients unlikely to respond to treatment who can thus be offered alternative treatments or entry into clinical trials.


Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Queratina-18/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pemetrexede , Estudos Prospectivos , Curva ROC , Resultado do Tratamento
6.
Lung Cancer ; 85(2): 186-90, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24854403

RESUMO

OBJECTIVES: The aim of this study was to investigate the clinical significance of cytology versus histology-based diagnosis among patients diagnosed with small cell lung cancer (SCLC). MATERIALS AND METHODS: Retrospective analysis of medical records of 443 patients with histologically or cytologically confirmed small cell lung carcinoma (SCLC) was performed. All patients received platinum-based chemotherapy regimens. Survival data (overall survival) were compared between patients with histology or cytology-based diagnosis in the overall study population as well as after stratification of patients according to disease stage (limited or extensive) at the time of diagnosis. RESULTS: Distribution of demographics and clinicopathological characteristics among the two groups ("histology" and "cytology") was similar. No statistically significant differences in the survival curves between the "histology" and "cytology" groups were found in the overall study population (log rank test, p=0.237), as well as in the subgroup of patients with limited disease (log rank test, p=0.474). In contrast, patients with histology-based diagnosis had a statistically significant longer survival as compared to those with cytology-based diagnosis in the extensive disease subgroup (log rank test, p=0.031), but this association was not retained after adjusting the analysis for demographics and clinical characteristics via a Cox regression model (HR=1.18, 95% CI: 0.96-1.44, p=0.110). CONCLUSION: The results of our study suggest that the type of diagnostic modality employed (histology or cytology-based) for the establishment of a diagnosis of SCLC may not have a significant effect on the overall survival of patients. Further studies are warranted to further investigate this important, yet rather unexplored, issue.


Assuntos
Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Idoso , Citodiagnóstico , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade
7.
Clin Colorectal Cancer ; 12(4): 267-274.e2, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24050852

RESUMO

BACKGROUND: Patients with colorectal cancer (CRC) with wild-type KRAS mutations are often treated with the endothelial growth factor receptor (EGFR) monoclonal antibody cetuximab. Despite the presence of a specific molecular target, most patients still do not derive benefit from this biological treatment. Our study explores the role of ephrin A2 (EphA2) receptor expression and of EGFR pathway mediators as predictors of cetuximab benefit. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor biopsy samples from 226 cetuximab-treated patients with CRC were studied for mRNA expression of insulin growth factor binding protein 2 (IGFBP2), insulin growth factor receptor 1 (IGF1R), cMET, EphA2, human epidermal growth factor receptor 2 (HER2), HER3, and HER4 by means of TaqMan reverse-transcribed polymerase chain reaction (RT-PCR). RESULTS: Of the 226 patients evaluable for exploratory analysis, 222 had complete data from follow-up visits. The univariate analysis revealed the following significant adverse prognostic factors for risk of death: high EphA2 mRNA levels (hazard ratio [HR], 1.61; P = .015), high HER2 mRNA levels (HR, 1.51; P = .045), and high IGF1R mRNA levels (HR, 1.56; P = .021). Low EphA2 tumor expression was significantly associated with objective response to cetuximab therapy. In multivariate analysis of a broad biomarker panel, factors with independent prognostic value included EphA2 mRNA levels (HR, 1.67; P = .029), high amphiregulin (AREG) mRNA levels in KRAS wild-type tumors (HR, 0.17; P < .0001), and high epiregulin (EREG) mRNA levels (HR, 0.38; P = .006). CONCLUSION: High EphA2 receptor expression in CRC was associated with a worse outcome in patients treated with cetuximab-based therapy. Prospective validation in treated and control patients is required to dissect the predictive from prognostic role in advanced CRC.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/análise , Neoplasias Colorretais/metabolismo , Efrina-A2/metabolismo , Transdução de Sinais/fisiologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Cetuximab , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Receptores ErbB/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
JOP ; 14(4): 354-8, 2013 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-23846926

RESUMO

Over the last twenty years, there is a limited number of effective cytotoxic or biological agents that managed to get approval in advanced pancreatic ductal adenocarcinoma. Despite numerous trials, investments in translational research and generally in health care, the survival of pancreatic cancer patients has improved by a few only months. This disappointing reality necessitates a better understanding of the pathogenesis of this disease and the identification of targetable alterations which might lead to development of more effective drugs or better combinations. At the 2013 Annual Meeting of the American Society of Clinical Oncology, few novel agents and new therapeutic concepts, tested in phase I studies in advanced pancreatic ductal adenocarcinoma, were presented. The first notable phase I study referred to the combination of chemotherapy with local delivery of silencing RNA against the K-ras mutation G12D, in advanced pancreatic ductal adenocarcinoma, which was well tolerated and promising (Abstract #4037). The second one referred to a combination of gemcitabine with pegylated recombinant human hyaluronidase (PEGPH20), an inhibitor of hyaluronan which as a matrix glycosaminoglycan is believed to play role in the reduced drug delivery to cancer (Abstract #4010). The other notable abstract was related to an early phase study which tested the safety and toxicity of arctigenin, a traditional herbal agent found in Arctium lappa Linné, administered as an oral formulation (GMS-01) in pancreatic ductal adenocarcinoma patient resistant to standard chemotherapy (Abstract #2559). The aforementioned early phase studies open new therapeutic approaches which deserve further testing in advanced pancreatic cancer.


Assuntos
Adenocarcinoma/terapia , Ensaios Clínicos Fase I como Assunto , Neoplasias Pancreáticas/terapia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Furanos/uso terapêutico , Humanos , Hialuronoglucosaminidase/administração & dosagem , Hialuronoglucosaminidase/química , Hialuronoglucosaminidase/genética , Lignanas/uso terapêutico , Mutação , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Polietilenoglicóis/química , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Interferência de RNA , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/química , Resultado do Tratamento , Proteínas ras/genética , Gencitabina
9.
JOP ; 14(4): 359-62, 2013 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-23846927

RESUMO

Despite advances and investments in translation research, clinical trials and health service in general, there is no significant impact on the survival of most patients diagnosed with advanced pancreatic adenocarcinoma. It is broadly recognized though that there is a small minority of patients who really benefit from particular treatments for reason usually not well understood. Light to this fact is gradually shed by developments in the field of pharmacogenomics, which plays pivotal role in what we call individualized medicine. In that perspective, it is of most importance to present the significant developments in pharmacogenomics announced in the recent 2013 American Society of Clinical Oncology Annual Meeting. First, the predictive role of hENT1, which codes for a gemcitabine transporter into cells, was highlighted and might help us decide whether we benefit from gemcitabine or 5-fluorouracil in the adjuvant setting (Abstract #4006). Second, authors presented the negative predictive role of SPARC stroma and cytoplasmic expression in patients treated with adjuvant gemcitabine (within the CONCO-001 study) as they reported poor outcome of those having high expression, not seen in patients on observation (Abstract #4016). Finally, a study which might be a basis for future strategies and as great food for scientific thought suggested that selection of cytotoxic treatment based on gene expression profiling is feasible in clinical practice and may help improve treatment efficacy as well as predict for drug resistance (Abstract #4017). Of course, there is a long way to go before implementation of these genomic findings, with the exception of hENT1 which seems to be close for clinical use.


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Farmacogenética/métodos , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Osteonectina/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Transcriptoma/efeitos dos fármacos , Resultado do Tratamento , Gencitabina
10.
JOP ; 13(4): 338-41, 2012 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-22797384

RESUMO

Despite improvements in the health service and the available treatment means, the outcome of the majority of patients with advanced pancreatic adenocarcinoma, even in the Western world, is disappointing. This fact necessitates invention and development of clinical and laboratory biomarkers that help us detect early enough those patients who have the worst prognosis, and who may benefit or not from our treatments and individualize thus our management accordingly. In the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, four interesting scientific works on biomarkers in pancreatic cancer were presented. Two of them presented new clinical data such as the correlation of hand and foot skin reaction with the prognosis of patients treated with capecitabine based treatment (Abstract #4023), and the independent association of early presentation of venous thromboembolic events with poor survival (Abstract #4037). The other two significant abstracts focused on new potential predictive laboratory biomarkers, such as the association of the baseline levels of serum albumin to benefit from bevacizumab enriched treatment (Abstract #4039) and the likely correlation of high insulin growth factor 1 (IGF-1) tissue expression to better prognosis in patients treated with the IGF-1 receptor monoclonal antibody (mAb) MK-0646 (Abstract #4054).


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab , Biomarcadores , Capecitabina , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/fisiologia , Tromboembolia Venosa/epidemiologia
11.
JOP ; 13(4): 345-8, 2012 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-22797386

RESUMO

Pancreatic cancer is a relatively rare malignancy with a very aggressive natural course, not restrained by the existing current treatments. At the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, the results of few phase I clinical studies on solid tumors and pancreatic cancer were presented. In particular, in the field of immunotherapy, a pilot phase I study tested for first time a carcinoembryonic antigen (CEA)-based vaccine (Abstract #2561) on patients with pancreatic adenocarcinoma and another one the optimal dose and efficacy of trabedersen, an inhibitor of tissue growth factor-beta 2 (TGF-ß2) aiming to enhance antitumor immune responses (Abstract #4034). Other phase I studies explored the pharmacokinetic and pharmacodynamic properties of an oral gemcitabine pro-drug (LY2334737; Abstract #2554), or of the combination of gemcitabine with sirolimus (Abstract #3096) or the combination of gemcitabine with an inhibitor of mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinase (ERK) (MEK 1/2; Abstract #4034).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Ensaios Clínicos Fase I como Assunto , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Humanos , Imunoterapia , Neoplasias Pancreáticas/imunologia , Sirolimo/administração & dosagem , Gencitabina
12.
JOP ; 13(4): 358-60, 2012 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-22797389

RESUMO

Despite the enormous advances in clinical research in oncology, the prognosis of pancreatic carcinoma remains poor. The therapeutic options in this type of cancer are very limited, with modest results at present. In the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, four interesting trials on the second line treatment of pancreatic cancer were presented. The first study (Abstract #4017) with a phase II design suggested that maintenance therapy with sunitinib, after a complete course of standard first line treatment, was feasible and effective while the second phase I/II study (Abstract #4034) evaluated the role of trabedersen, an agent that inhibits TGF-ß2 expression. Finally, the efficacy and toxicity of lapatinib combined with either FOLFOX (Abstract #e14533) or capecitabine (Abstract #e14569) were examined in the second line setting of pancreatic cancer.


Assuntos
Neoplasias Pancreáticas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina , Ensaios Clínicos como Assunto , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Lapatinib , Leucovorina/administração & dosagem , Oligodesoxirribonucleotídeos/uso terapêutico , Compostos Organoplatínicos/administração & dosagem , Neoplasias Pancreáticas/patologia , Quinazolinas/administração & dosagem , Tionucleotídeos/uso terapêutico
13.
Clin Lung Cancer ; 13(6): 408-15, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22694791

RESUMO

Endobronchial ultrasound (EBUS) technology is a relatively new bronchoscopic method of visualizing the tracheobronchial tree, the surrounding pulmonary parenchyma, and the mediastinal structures, with a particular role in lung cancer diagnosis, staging, and treatment. There are 2 types of probes used in EBUS: the peripheral or radial probe (RP) and the linear or convex probe (CP) EBUS, which have technical differences and distinct diagnostic abilities. Both are used for EBUS-guided biopsies and transbronchial needle aspirations (TBNA), which increases the diagnostic yield over conventional bronchoscopic techniques, thus providing advanced information on staging, diagnosis, and treatment. Complications of EBUS are rare, and they are usually related to the underlying biopsy procedure and the operator's experience. EBUS examination duration is usually short, and it can be performed as an outpatient procedure. Interestingly, EBUS combinations with other current and evolving techniques, eg, electromagnetic navigation, are feasible and have a role in therapeutic interventions and molecular diagnostics. In conclusion, EBUS is a safe and accurate technique that is comparable with current criterion standard procedures, eg, mediastinoscopy. More training is required for the vast majority of respiratory physicians, and precise diagnostic algorithms are needed so that more patients benefit from this development.


Assuntos
Broncoscopia/métodos , Endossonografia/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Biópsia por Agulha/métodos , Broncoscópios , Broncoscopia/efeitos adversos , Endossonografia/efeitos adversos , Desenho de Equipamento , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias
14.
Dermatology ; 224(4): 315-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22699716

RESUMO

BACKGROUND: Papulopustular eruption (PPE) is the most common cutaneous side effect of epidermal growth factor receptor inhibitors (EGFRIs). OBJECTIVE: To document the efficacy and safety of pulsed azithromycin doses in the treatment of EGFRI-related PPE. METHODS: A retrospective analysis of patients under EGFRIs who exhibited at least grade 2 PPE and were intolerant or resistant to tetracyclines was performed. Treatment consisted of pulsed azithromycin doses of 500 mg daily for 3 consecutive days per week for at least 2 weeks. RESULTS: Treatment with azithromycin showed a significant reduction in the number of lesions in 18/20 patients, with 11 showing complete resolution of the rash. No significant side effects were recorded. We did not observe any interactions with the targeted biological agents or any obvious compromise of the anticancer treatment. CONCLUSIONS: Weekly pulses of azithromycin are effective and promote increased patient adhesion to the treatment. A prospective study is needed to confirm efficacy and safety of this convenient treatment.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Toxidermias/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Exantema/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Cetuximab , Toxidermias/etiologia , Cloridrato de Erlotinib , Exantema/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Panitumumabe , Pulsoterapia , Quinazolinas/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo
15.
JOP ; 13(2): 166-8, 2012 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-22406592

RESUMO

The standard current treatment options in advanced pancreatic cancer have demonstrated minimal or modest only efficacy for the majority of patients. Unfortunately, the mortality and morbidity remain high crying out for better treatments and results. With the exception of erlotinib, which received approval by the Food and Drug Administration of the United States in 2005, no other novel agents have since been added in our treatment quiver. Therefore, the search for novel approaches continuous at the laboratory and clinical level. At the 2012 American Society of Clinical Oncology Gastrointestinal Symposium, results of some interesting early phases clinical studies were presented. First, in Abstract #198, toxicity and efficacy results from the phase I/II study of cixutumumab, an insulin growth factor-1 receptor (IGF-1R) antibody combined with the standard gemcitabine and erlotinib treatment were presented, but the outcomes suggest no real clinical benefit. Second, the early safety and clinical data from the novel monoclonal antibody (ensituximab) against the mucin epitope NPC-1C in pancreatic and colon cancer patients were presented (Abstract #233) and again no particular efficacy was observed. Finally, interesting results which definitely deserve further exploration were presented in Abstract #211, which tested the combination of ipilimumab, an antibody against the cytotoxic T-lymphocyte antigen 4 (CTLA-4), with a cell-based vaccine transfected with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene in advanced refractory pancreatic cancer. Though, it seems we have not yet found the culprit and the solution of this devastating disease, a small step forward might have been achieved.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Quinazolinas/uso terapêutico , Anticorpos Monoclonais Humanizados , Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Cloridrato de Erlotinib , Humanos , Ipilimumab , Neoplasias Pancreáticas/mortalidade , Inibidores de Proteínas Quinases/uso terapêutico , Radiossensibilizantes/uso terapêutico , Gencitabina
16.
JOP ; 13(2): 177-9, 2012 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-22406595

RESUMO

The current achievements in pancreatic cancer diagnosis and treatment are disappointing for patients and clinicians alike. Still, in the dawn of 2012, most patients are diagnosed at a late stage where cure is not feasible, with the majority going to succumb within the same year of diagnosis. Thus, the only hope for early and diagnosis and radical treatment is the invention of diagnostic and prognostic tests which might predict accurately patients who may develop this disease and those who have the most aggressive potential, so clinician adopt the appropriate strategy. In this paper we summarize the findings from the three most interesting research abstract as presented at the 2012 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. In particular, we focus on Abstract #160 which shows the diagnostic utility of microRNA serum profiling in pancreatic cancer patients, on Abstract #201 which suggests a potential prognostic role of transforming growth factor (TGF)-beta pathway in advanced pancreatic cancer, and on Abstract #165 which shows that protein S100A4 might be a new, potentially useful, predictive biomarker of gemcitabine efficacy.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Pesquisa Translacional Biomédica/tendências , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Neoplasias Pancreáticas/metabolismo
17.
Anticancer Res ; 31(9): 2971-4, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21868546

RESUMO

OBJECTIVE: To assess the efficacy of gemcitabine based chemotherapy in heavily pre-treated patients with advanced colorectal cancer. PATIENTS AND METHODS: Patients, who had been treated with gemcitabine 1250-2000 mg/m² biweekly in combination with capecitabine 1700-2000 mg/m²/day, d1-7 every two weeks were retrospectively reviewed. All the patients had previously received at least three chemotherapy regimens and 12 (55%) had also received a 4th line regimen. All the patients had been treated with a monoclonal antibody either against vascular endothelial growth factor receptor (VEGFR) or endothelial growth factor receptor (EGFR) (only if wild-type KRAS). The patients had had blood tests weekly, carcinoembryonic antigen (CEA) level measurement every 4 weeks and radiological assessment of their disease with CT scans every 8/9 weeks. RESULTS: Twenty two patients were included; male-female, 14:8; age ranged from 43-73 years. The majority of the patients (17/22) had performance status (PS) ECOG 0-1 and the remaining patients (5/22) had PS 2 at the time of initiation of the gemcitabine-based regimen. Thirteen patients demonstrated a clinical benefit (2 partial response, 2 minor response, 9 stable disease), 6 patients progressed and 2 were not evaluable. CONCLUSION: Gemcitabine has a modest activity in heavily pre-treated colorectal cancer patients and may be an option in good performance status patients.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Desoxicitidina/análogos & derivados , Adulto , Idoso , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação , Gencitabina
18.
JOP ; 12(4): 325-9, 2011 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-21737888

RESUMO

Appropriate identification and validation of biomarkers as well as pharmacogenetics are important in formulating patient-oriented, individualized chemotherapy or biological therapy in cancer patients. These markers can be especially valuable in pancreatic cancer, where high mortality and complex disease biology are frequently encountered. Recently, several advances have been made to further our knowledge in this specific area of pancreatic cancer. In the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting, researchers have presented several interesting results in biomarkers development: the identifications of 9 single nucleotide polymorphisms (SNPs) that is associated with positive efficacy of gemcitabine (Abstract #4022); the introduction of circulating tumor cells as a prognostic markers in pancreatic adenocarcinoma (Abstract #e14657); the re-affirmation of plasma cytidine deaminase (CDA) as a positive predictive markers for gemcitabine efficacy, as well as the postulations that CDA*3 as a potential genotype marker to predict gemcitabine responses (Abstract #e14645); and finally the retrospective tumor tissues analysis in the Arbeitsgemeinschaft Internistische Onkologie (AIO) trial in an attempt for epidermal growth factor receptor (EGFR) pathway biomarker identifications (Abstract #4047).


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Neoplasias Pancreáticas/genética , Farmacogenética/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Biomarcadores Farmacológicos/análise , Biomarcadores Farmacológicos/metabolismo , Biomarcadores Tumorais/análise , Chicago , Congressos como Assunto , Regulação Neoplásica da Expressão Gênica , Humanos , Illinois , Oncologia/métodos , Oncologia/organização & administração , Modelos Biológicos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Sociedades Médicas , Estados Unidos
19.
JOP ; 12(4): 339-42, 2011 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-21737891

RESUMO

Despite the extensive research, mounting knowledge in the cancer field and enormous investments, pancreatic cancer remains a rather incurable disease with aggressive natural course and high mortality rate. The very slow progress is a result of the complex pathogenesis of this disease, which prevents us from targeting the culprit and making a step forward. Therefore, the field is still unexplored and this is a real challenge and opportunity for new ideas and novel approaches. In this paper, we will present the most interesting studies in the first line pancreatic cancer setting, presented at the American Society of Clinical Oncology (ASCO) 2011 Annual Meeting. While there are few studies testing the role of combining the cytotoxic S-1 and gemcitabine, the majority of the studies are examining the safety and impact of adding to the classic gemcitabine treatment novel molecular agents which target key pathways or overexpressed proteins.


Assuntos
Adenocarcinoma/terapia , Oncologia/tendências , Terapia Neoadjuvante/tendências , Neoplasias Pancreáticas/terapia , Adenocarcinoma/patologia , Chicago , Congressos como Assunto , Humanos , Oncologia/métodos , Modelos Biológicos , Terapia Neoadjuvante/métodos , Metástase Neoplásica , Neoplasias Pancreáticas/patologia , Sociedades Médicas , Estados Unidos
20.
JOP ; 12(2): 117-9, 2011 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-21386634

RESUMO

Neuroendocrine tumors of pancreas (PNET) are very rare, consisting of heterogeneous histological subtypes with a variable natural history and different clinical manifestations. Although the vast majority of these neoplasms are sporadic, it is possible to be part of a genetic syndrome such as multiple endocrine neoplasia 1 (MEN-1) or tuberous sclerosis (TSC). When systemic treatment is required the options are limited and management strategy is generally based on experts' consensus or clinical experience. The prognosis is usually better than in pancreatic adenocarcinoma, though poorly differentiated PNET behave aggressively and survival is shortened. Since last year, there has been a significant advance in the management of PNET, after reported data confirmed the efficacy of everolimus, an mTOR inhibitor, in patients with advanced disease. At the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Symposium, updated results of the phase III trial (RADIANT-3) regarding the efficacy of everolimus in PNET (Abstract #158) were reported, along with the results of a subgroup analysis of the Japanese patients enrolled in this study (Abstract #289). Another agent with promising activity in PNET which will be discussed in this review is sunitinib, a biological agent with multikinase inhibitor properties (Abstract #244).


Assuntos
Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Sirolimo/análogos & derivados , Antineoplásicos/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Everolimo , Humanos , Imunossupressores/uso terapêutico , Indóis/uso terapêutico , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Pirróis/uso terapêutico , Sirolimo/uso terapêutico , Sunitinibe , Resultado do Tratamento
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