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1.
Ann Oncol ; 22(7): 1528-1534, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21212155

RESUMO

BACKGROUND: Sorafenib is a small-molecule multitargeted kinase inhibitor that blocks the activation of C-RAF, B-RAF, c-KIT, FLT-3, RET, vascular endothelial growth factor receptor 2 (VEGFR-2), VEGFR-3 and platelet-derived growth factor receptor ß. The aim of this multicenter, randomized phase II study was to evaluate clinical activity and safety of sorafenib in combination with erlotinib or gemcitabine in unselected untreated elderly patients with non-small-cell lung cancer (NSCLC). METHODS: The trial was designed to select the most promising sorafenib-containing combination in previously untreated elderly (≥70 years) stage IIIB or IV NSCLC patients, with performance status of zero to two. Patients were randomly assigned to one of the following combinations: gemcitabine, 1200 mg/m(2) days 1 and 8, every 21 days, for a maximum of six cycles, plus sorafenib, 800 mg/day, until disease progression or unacceptable toxicity (arm 1); or erlotinib, 150 mg/day, plus sorafenib, 800 mg/day, until disease progression or unacceptable toxicity (arm 2). A selection design was applied with 1-year survival rate as the primary end point of the study, requiring 58 patients. RESULTS: Sixty patients were randomly allocated to the study (31 patients in arm 1 and 29 patients in arm 2). After a median follow-up of 15 months, 10 patients [32%, 95% confidence interval (CI) 16% to 49%] in arm 1 and 13 patients (45%, 95% CI 27% to 63%) in arm 2 were alive at 1 year. Median overall survival was 6.6 and 12.6 months in arm 1 and arm 2, respectively. Observed toxic effects were consistent with the expected drug profiles. CONCLUSIONS: The combination of erlotinib and sorafenib was feasible in elderly patients with advanced NSCLC and was associated with a higher 1-year survival rate than the other arm. According to the selection design, this combination warrants further investigation in phase III trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma Bronquioloalveolar/tratamento farmacológico , Adenocarcinoma Bronquioloalveolar/mortalidade , Idoso , Idoso de 80 Anos ou mais , Benzenossulfonatos/administração & dosagem , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Cloridrato de Erlotinib , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas/administração & dosagem , Quinazolinas/administração & dosagem , Sorafenibe , Taxa de Sobrevida , Resultado do Tratamento , Gencitabina
2.
Crit Rev Oncol Hematol ; 66(2): 155-62, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18083041

RESUMO

Advances in the knowledge of tumor biology and mechanisms of oncogenesis has granted the singling out of several molecular targets for non-small cell lung cancer (NSCLC) treatment. Among these targets, epidermal growth factor receptor (EGFR), or HER1, has received particular attention in lung cancer treatment. Erlotinib, an orally available inhibitor of EGFR tyrosine kinase in a phase III randomized placebo-controlled trial (BR.21), has been proven to prolong survival in NSCLC patients after first or second line chemotherapy. Skin rash is the most common adverse event associated with erlotinib treatment and it is often cause of negative impact on patients' quality of life. There is no specific treatment for this toxicity due to the lack of evidence-based data and recommendations. A panel of Italian oncologists, who had participated to clinical trials and to the Expanded Access Program for erlotinib in NSCLC treatment, and dermatologists with experience with cutaneous toxicity from EGFR inhibitors, attended a Meeting held in Rome on December 2006 to discuss skin rash from erlotinib and to provide suggestions for managing this frequent side-effect.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Exantema/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Antineoplásicos/administração & dosagem , Pesquisa Biomédica , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Fármacos Dermatológicos/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Receptores ErbB/metabolismo , Cloridrato de Erlotinib , Exantema/tratamento farmacológico , Exantema/patologia , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/mortalidade , Guias de Prática Clínica como Assunto , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Resultado do Tratamento
3.
Crit Rev Oncol Hematol ; 60(1): 76-86, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16843002

RESUMO

New blood vessel formation, known as angiogenesis is a fundamental event in the process of tumor growth and metastatic dissemination. Due to its central role in tumor angiogenesis, the vascular endothelial growth factor (VEGF) and its receptor have been a major focus of basic research and drug development in the field of oncology, including the treatment of non-small cell lung cancer (NSCLC). Approaches targeting VEGF include monoclonal antibodies and vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs). Bevacizumab (Avastin) is an anti-VEGF recombinant humanized monoclonal antibody. A very recent randomized phase III trial demonstrated a statistically significant advantage in median survival favouring the combination of bevacizumab plus chemotherapy versus chemotherapy alone in the treatment of advanced non-squamous NSCLC. This study represents the first evidence of superior efficacy of targeted therapy combined with chemotherapy over chemotherapy alone in the treatment of NSCLC. ZD6474 is an orally bioavailable inhibitor of VEGFR-2 tyrosine kinase. First evidences of antitumor activity and its excellent toxicity profile make it a promising targeted agent for the treatment of NSCLC. A recent phase I/II study examined the combination of Epidermal Growth Factor Receptor (EGFR)-TKI erlotinib and bevacizumab in patients with non-squamous stage IIIB/IV NSCLC. Data on antitumor activity of this combination have to be considered very promising. Clinical trials of multiple targeted therapy may represent the second generation studies in the treatment of NSCLC.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Modelos Biológicos , Neovascularização Patológica/tratamento farmacológico
4.
Ann Oncol ; 17 Suppl 5: v72-8, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16807469

RESUMO

The elderly and patients with Performance Status (PS) of 2, constitute the so-called special patient population. The tolerability of chemotherapy in this population is globally worse, and treatment approaches should be different. Platinum-based combination chemotherapy is currently recommended as the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its role in special patient population is controversial. The best treatment for elderly patients with advanced NSCLC is still debated. In the first randomized study dedicated to elderly NSCLC patients, single-agent vinorelbine showed superiority over supportive care alone, both in terms of survival and quality of life. In a large randomized trial, gemcitabine plus vinorelbine failed to show any advantage over either agent alone. Subset analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with an acceptable increase in toxicity for elderly patients. However, the role of platin-based chemotherapy needs to be defined in prospective randomised trials. With the current evidence, single-agent chemotherapy with a third-generation drug (vinorelbine, gemcitabine, taxanes) should be the recommended option for non-selected elderly patients with advanced NSCLC. Also for PS2 patients there is no consensus on standard treatment. On the basis of current evidence, chemotherapy treatment appears justified for patients with advanced NSCLC and PS2. Single-agent chemotherapy (gemcitabine, vinorelbine, taxanes) could be the preferred option, although carboplatin-based or low-dose cisplatin-based doublets may represent alternative options. Stronger evidence is expected from new clinical research specifically focused on PS2 patients. High priority should be given to the evaluation of tolerability and efficacy of platinum-based combinations and role of new targeted therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Progressão da Doença , Humanos , Neoplasias Pulmonares/patologia , Cuidados Paliativos , Grupos Populacionais , Índice de Gravidade de Doença
5.
Expert Rev Clin Pharmacol ; 9(12): 1571-1581, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27623999

RESUMO

INTRODUCTION: Lung cancers remain the principal cause of death cancer-related worldwide with a poor survival rate at five years from diagnosis. In patients with NSCLC harboring specific genetic alterations the anti EGFR TKIs and the ALK TKIs have improved the response rate and the quality of life compared to standard platinum-based chemotherapy. New approaches possibly applicable at the major of patients are needed. Areas covered: The discovery that the immune system plays a fundamental role in the fight against cancer. The cancer cells use mechanisms able to avoid the immune control has led to the development of drugs able to overcome this escape route. The best known checkpoint pathways are the CTLA-4 and PD-1/PD-L1; they suppress T-cell activity in different ways: CTLA-4 regulates T-cell activity at an early stage whereas PD-1 regulates later effector T-cell activity within tissue and tumors. The best characterized checkpoint inhibitors in advanced NSCLC setting are ipilimumab and tremelimumab, (anti-CTLA-4 antibodies), nivolumab and pembrolizumab (anti-PD-1 antibodies), atezolizumab and durvalumab (anti-PD-L1 antibodies). Nivolumab and pembrolizumab have received the FDA and EMA approval for the treatment of NSCLC in second-line setting. Expert commentary: The role played by tumor microenvironment may be the next area of research to overcome the resistance at the checkpoint inhibitors as well as the identification of biomarkers to better select patients. In addition checkpoint inhibitors are investigate in combination with other agent involved in immune control with promising results in solid tumors.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia/métodos , Biomarcadores Tumorais , Vacinas Anticâncer , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos
6.
Curr Med Chem ; 12(3): 297-310, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15723620

RESUMO

Breast cancer arises in about 48% of patients older than 65 years and more than 30% occurs in those over 70 years being the leading cause of cancer-related death in women older than 65. Elderly patients tolerate chemotherapy poorly compared to their younger counterpart because of progressive reduction of organ function and comorbidities related to age. For this reason, the elderly have been excluded from or underrepresented in most cancer studies and, in clinical practice, they often receive inadequate and untested treatments. For adjuvant chemotherapy, a low percentage of patients over 70 years of age were included in few trials and always in a proportion much lower than the prevalence of cancer in that age group. Adjuvant chemotherapy, preferably including an anthracycline especially in patients with HER-2/neu-positive tumours, seems to be beneficial in older women who have substantial risk of dying of breast cancer. To date even if there is no specifically randomised study, single-agent chemotherapy probably might be considered a reasonable treatment for advanced breast cancer in the elderly. One of the actual main field of clinical research in the treatment of breast cancer is the role of targeted therapies. Chronologic age is a risk factor for toxicities such as myelosuppression and mucositis, and older patients may require more supportive care. In order to plan medical treatment in breast cancer elderly patients is mandatory to practice a comprehensive geriatric assessment that includes evaluation of comorbidities, functional dependence, socio-economic, emotional and cognitive conditions, an estimate of life expectancy and recognition of frailty. The authors review the literature regarding age-specific chemotherapeutic issues in the management of breast cancer elderly patients.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Idoso , Envelhecimento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Comorbidade , Interações Medicamentosas , Idoso Fragilizado , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Ann Oncol ; 16 Suppl 4: iv110-115, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15923410

RESUMO

Lung cancer is the most common cause of cancer deaths in both men and women worldwide and has a poor prognosis. Non-small-cell lung cancer (NSCLC) represents approximately 80% of all lung cancers. Surgery is the only curative treatment of NSCLC but only 15-20% of tumours can be radically resected with a survival of about 40% at 5 years. Considering these disappointing results NSCLC is one of the most frequent subjects of clinical research worldwide. Italy is playing an important role in the clinical research of NSCLC performing phase I, II and III trials, prevalently by cooperative groups, and achieving important results that contributed to define the standard treatment for NSCLC patients. In particular, Italy is leader in the clinical research of the treatment of advanced NSCLC elderly patients. Today, large controlled clinical trials are ongoing. In this paper we analyse and discuss the main trials performed by Italian groups in the fields of NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Ensaios Clínicos como Assunto/métodos , Feminino , Humanos , Itália , Neoplasias Pulmonares/mortalidade , Masculino , Radioterapia Adjuvante , Taxa de Sobrevida , Resultado do Tratamento
8.
Crit Rev Oncol Hematol ; 47(3): 261-71, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12962900

RESUMO

In the last few years the knowledge of molecular oncology has led to the development of many new biological agents whose targets are extracellular or intracellular molecules involved in the main signalling pathways that play major roles in cancer development. These agents represent a new approach to gastrointestinal malignancies, as for many other types of tumors; preliminary data show that targeted therapy may enhance activity of chemotherapeutic agents (i.e. cetuximab in metastatic colorectal cancer (CRC)) or be active as monotherapy (i.e. imatinib in gastro-intestinal stromal tumors). Despite the encouraging preclinical results, the majority of these compounds have not yet produced convincing clinical results. However, these new agents raise a new challenge in the treatment of gastrointestinal cancers, especially for CRC.


Assuntos
Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias Gastrointestinais/tratamento farmacológico , Alquil e Aril Transferases/antagonistas & inibidores , Inibidores da Angiogênese , Antineoplásicos/farmacologia , Ciclo-Oxigenase 2 , Receptores ErbB/antagonistas & inibidores , Farnesiltranstransferase , Humanos , Isoenzimas/antagonistas & inibidores , Inibidores de Metaloproteinases de Matriz , Proteínas de Membrana , Prostaglandina-Endoperóxido Sintases
9.
Crit Rev Oncol Hematol ; 51(1): 45-53, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15207253

RESUMO

Lung cancer is the leading world-wide cause of cancer death. Small-cell lung cancer (SCLC) accounts for 20-25% of lung carcinomas. Chemotherapy is the cornerstone of treatment of SCLC. In limited disease, median survival is about 12-16 months with 4-5% of long-term survivors, in extensive disease median survival is 7-11 months. Improving the survival rate of patients with SCLC requires a better understanding of tumour biology and the subsequent development of novel therapeutic strategies. Several targeted agents have been introduced into clinical trials in SCLC and some phase III studies have already produced definitive results. Currently, the minority of these new agents offers a promise of improved outcomes, and negative results are more commonly reported than positive ones. To date, no targeted therapy has been approved for use in the treatment of patients with SCLC. This review will focus on the main novel biologic agents investigated in the treatment of SCLC.


Assuntos
Antineoplásicos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Carcinoma de Células Pequenas/terapia , Neoplasias Pulmonares/terapia , Oligorribonucleotídeos Antissenso/uso terapêutico , Carcinoma de Células Pequenas/irrigação sanguínea , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/patologia , Ensaios Clínicos Fase III como Assunto , Sistemas de Liberação de Medicamentos , Humanos , Imunoterapia Ativa , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Neovascularização Patológica/terapia
10.
Curr Med Chem ; 9(16): 1487-95, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12171559

RESUMO

Non-small cell lung cancer (NSCLC) may be considered typical of advanced age. More than 50% of NSCLC patients are diagnosed over the age of 65 and approximately one-third of all patients with non-small cell lung cancer (NSCLC) are over the age of 70. Elderly patients tolerate chemotherapy poorly as compared to their younger counterparts, because of the progressive reduction of organ function and comorbidities related to age. For this reason, these patients are often not considered eligible for aggressive cisplatin-based chemotherapy, the standard medical treatment of advanced NSCLC. At present, for early stages of the disease there are no indications for adjuvant and neoadjuvant chemotherapy. Combined chemo-radiotherapy in locally advanced disease increases toxicity and seems to determine no survival advantage as compared to the radiation therapy alone. In advanced disease, single agent vinorelbine has proven to be active and well-tolerated, and compared to best supportive care, improves survival and perhaps even the quality of life. Gemcitabine is active and well tolerated as well. Taxanes are in advanced phase of evaluation. A phase III randomized trial showed that polychemotherapy with gemcitabine and vinorelbine does not improve any outcome as compared to single agent chemotherapy with vinorelbine or gemcitabine. In clinical practice, single agent chemotherapy should remain the standard treatment. The two main research-lines to be explored in the near future are the introduction of biological agents in the treatment schemes and the development of specifically designed schedules of cisplatin-based regimens. However, practicing a multidimensional geriatric awsessment for individualized treatment choice in NSCLC elderly patients is mandatory.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Ensaios Clínicos como Assunto , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Humanos , Neoplasias Pulmonares/mortalidade , Fatores de Risco , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vinorelbina , Gencitabina
11.
Curr Med Chem ; 9(21): 1851-8, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12369871

RESUMO

Lung cancer is the leading cause of death from cancer in most developed nations. The most common type of lung cancer is of non-small cell histology, representing approximately 80% of the total. Despite aggressive treatments in early stages and improvement of polychemotherapy outcomes in advanced disease, the five years survival rate for lung cancer remains under 15%. Fortunately, our improved knowledge of tumor biology and mechanisms of oncogenesis suggests several new potential targets for clinical research in cancer therapy. A substantial body of evidence indicates that cyclooxigenase (COX)-2 and prostaglandins (PGs) play an important role in tumorigenesis. Mechanisms involved in COX-2 participation in tumorigenesis and tumor growth include xenobiotic metabolism, angiogenesis stimulation, inhibition of immune surveillance and inhibition of apoptosis. COX-2 is frequently overexpressed in bronchial premalignancy, lung adenocarcinoma and squamous cell carcinoma and COX-2 overexpression is a marker of poor prognosis in surgically resected stage I non-small cell lung cancer. Treatment with COX-2 inhibitors reduces the growth of NSCLC cells in vitro and in xenograft studies. Recent studies have defined some of the mechanisms involved in COX-2 participation in NSCLC development and diffusion. These evidences support the hypothesis that selective COX-2 inhibitors (coxibs) may prove beneficial in the prevention and treatment of NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Isoenzimas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Prostaglandina-Endoperóxido Sintases/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/prevenção & controle , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Humanos , Isoenzimas/biossíntese , Isoenzimas/fisiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/prevenção & controle , Proteínas de Membrana , Invasividade Neoplásica/patologia , Prostaglandina-Endoperóxido Sintases/biossíntese , Prostaglandina-Endoperóxido Sintases/fisiologia
12.
Anticancer Res ; 21(6A): 4179-83, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11911315

RESUMO

UNLABELLED: A phase II trial was undertaken to test the activity and toxicity of carboplatin (300 mg/m2, i.v. day 1) + epirubicin (75 mg/m2, i.v. day 1) + VP-16 (100 mg/m2, i.v. days 1 to 3) + lenograstim (5 mcg/kg, s.c. days 6 to 15) administered every 3 weeks for 4 cycles and subsequent chest irradiation (50 Gy) + daily carboplatin (25 mg/m2) in the first-line treatment of adults affected by limited small cell lung cancer (SCLC). PATIENTS AND METHODS: A single-stage phase II design was used; the complete response (CR) rate after chest radiotherapy was the primary end-point. Twenty-three CRs were required out of 38 patients to consider the treatment worthy of further study. Prophylactic cranial irradiation (PCI) was planned in case of CR. Patients aged < or = 70 were eligible if they had limited SCLC, a performance status not worse than 2 by the ECOG scale and no prior chemotherapy or radiotherapy. RESULTS: From January 1995 to April 1999, 33 patients were enrolled; the median age was 60 years. All the patients started chemotherapy; 23 patients received chest irradiation and concurrent daily carboplatin; 11 patients also received PCI. Toxicity was generally mild. Sixteen CRs (48.5%, 95% CI: 30.8-66.5) were recorded; the objective response rate was 72.7% (95% CI: 54.5-86.7). The median time-to-progression was 7.9 months (95% CI: 6.5-10.4). The median-survival was 10.7 months (95% CI: 9.2-16.1). CONCLUSION: Induction chemotherapy with carboplatin + epirubicin + VP-16 followed by chest irradiation plus concurrent daily carboplatin is well-tolerated but not sufficiently active to warrant further study in the treatment of patients with limited SCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Terapia Combinada , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Lenograstim , Masculino , Pessoa de Meia-Idade , Radiossensibilizantes/administração & dosagem , Radiossensibilizantes/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos
13.
Minerva Chir ; 49(5): 481-7, 1994 May.
Artigo em Italiano | MEDLINE | ID: mdl-7970049

RESUMO

On the basis of the observation of one case of delayed presentation of traumatic diaphragmatic rupture of the left side with a late diaphragmatic hernia, the authors examine the evolution of the occurrence of this pathology during the last 20 years. The clinical signs and the modality of presentation of the lesions of delayed diagnosis appear absolutely non specific. Incorrect interpretation of the X-ray or only intermittent hernial symptoms are frequent reasons for incorrect diagnosis. Also the initially non recognition of the possible manifestation of the diaphragmatic hernia following blunt or penetrating injuries is usually because the practitioner has not sought it. The diaphragmatic domes must be systematically explored during the laparotomy or thoracotomy performed for thoraco-abdominal trauma. Surgical treatment of long-standing post-traumatic diaphragmatic hernia is the same as that applicable in the recent hernias.


Assuntos
Hérnia Diafragmática Traumática/diagnóstico , Acidentes de Trânsito , Feminino , Hérnia Diafragmática Traumática/etiologia , Hérnia Diafragmática Traumática/cirurgia , Humanos , Pessoa de Meia-Idade , Fatores de Tempo
14.
Minerva Chir ; 51(10): 849-53, 1996 Oct.
Artigo em Italiano | MEDLINE | ID: mdl-9082217

RESUMO

Pseudomembranous colitis is an uncommon pathology although the number of cases recorded has risen steadily over the past decades. It is closely correlated with antibiotic treatment and above all affects immunodepressed subjects. It is manifested by a wide variety of clinical symptoms, ranging from simple diarrhea to acute abdomen. The latter, although fortunately extremely rare, often requires surgical therapy.


Assuntos
Enterocolite Pseudomembranosa/cirurgia , Adulto , Humanos , Masculino
15.
Ann Ital Chir ; 63(2): 141-5, 1992.
Artigo em Italiano | MEDLINE | ID: mdl-1503370

RESUMO

The authors report their results of a prospective study on 1182 patients who underwent surgical operation relatively on postoperative infections. Studied variables were: structural and anamnestic: sex, age, smoking, drinking; clinical: evidence of functional changes in various organs, as assessed upon clinical basis and laboratory results; pertinent to surgical intervention: entity, duration, anaesthesia; during and early-after-surgery complications (until discharge or within 30 days since intervention). Stepwise logistic regression model was applied to this set of preoperative and operative factors, four of which were found significantly correlate with postoperative infections: bacterial contamination during surgery, duration surgical intervention greater than 120', cholestasis, serum albumin.


Assuntos
Infecção Hospitalar/etiologia , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Idoso , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia
16.
Ann Ital Chir ; 64(4): 399-406, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8154664

RESUMO

Nine patients with tumors of the duodenum and the jejunum are described herein and the Literature is reviewed. Of the six patients with a duodenal tumor, five had an adenocarcinoma and one a Brunner's gland adenoma. A predominance of inframpullary tumors was observed within the duodenum. Jaundice and abdominal pain were, respectively, the most common presenting symptoms of the tumors localized in the periampullary and inframpullary region. Treatment was curative in four and palliative in two cases. Duodenopancreatectomy was the treatment of choice for periampullary tumors whereas segmental resection was performed in the only resectable distal duodenal tumor. Of the three patients with jejunal neoplasms, one had an adenocarcinoma arising in the efferent loop of a Billroth II gastrojejunostomy performed 40 years before and two had an high malignant lymphoma. All three the tumors could be resected. According to the Literature, our results show that: 1. The diagnosis of duodeno-jejunal tumors is usually late: 2. Although of critical importance in the improvement of the overall diagnostic accuracy, endoscopy may be inconclusive or even misleading if the entire duodenum is not explored; 3. If duodenopancreatectomy is mandatory for periampullary tumors, segmental resection seems to be an adequate procedure for tumors of the distal duodenum since it does not ignore lymphatic nodes, can be easily performed and has a low postoperative complication rate.


Assuntos
Neoplasias Duodenais/cirurgia , Neoplasias do Jejuno/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Curr Cancer Drug Targets ; 12(3): 289-99, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22229249

RESUMO

Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85% of all new lung cancer diagnosis. The majority of people with NSCLC are unsuitable for surgery since most patients have metastatic disease at diagnosis. About 60% of brain metastases arise from lung cancer. Therapeutic approaches to brain metastases include surgery, whole brain radiotherapy (WBRT), stereotactic radiosurgery, chemotherapy and new biologic agents. Angiogenesis is essential for the development and progression of cancer, and vascular endothelial growth factor (VEGF) is a critical mediator of tumour angiogenesis. One of the targeted approaches most widely studied in the treatment of NSCLC is the inhibition of angiogenesis. Bevacizumab, an anti-VEGF recombinant humanized monoclonal antibody, is the first targeted agent which, when combined with chemotherapy, has shown superior efficacy versus chemotherapy alone as first-line treatment of advanced non-squamous NSCLC patients. Patients with central nervous system (CNS) metastases have initially been excluded from bevacizumab trials for the risk of cerebral haemorrhage as a result of the treatment. Nevertheless, the available data suggest an equal risk of intracranial bleeding in patients with CNS metastases treated with or without bevacizumab therapy. Several other anti-angiogenetic drugs are being investigated in the treatment of advanced NSCLC patients, but results of their activity specifically in CNS metastases are still lacking. This review will focus on the potential role of bevacizumab and other anti-angiogenetic agents in the treatment of brain metastases from NSCLC.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Sistemas de Liberação de Medicamentos/tendências , Neoplasias Pulmonares/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Neoplasias Encefálicas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Sistemas de Liberação de Medicamentos/métodos , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Neovascularização Patológica/patologia , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
Curr Med Chem ; 19(20): 3337-52, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22664249

RESUMO

Lung cancer continues to be the leading cause of cancer death worldwide. Among lung cancers, 80% are classified as nonsmall- cell lung cancer (NSCLC) and are mostly diagnosed at an advanced stage (either locally advanced or metastatic disease). In the last years, the discovery of the pivotal role in tumorigenesis of the Epidermal Growth Factor Receptor (EGFR) has provided a new class of targeted therapeutic agents: the EGFR tyrosine kinase inhibitors (EGFR-TKIs). Since the first reports of an association between somatic mutations in EGFR exons 19 and 21 and response to EGFR-TKIs, treatment of advanced NSCLC has changed dramatically. Histologic profile, clinical characteristics, and mutational profile of lung carcinoma have all been reported as predictive factors of response to EGFR-TKIs and other targeted therapies. In advanced NSCLC patients harboring EGFR mutations, the use of EGFR TKIs in first-line treatment has provided an unusually large progression-free survival (PFS) benefit with a negligible toxicity when compared with cytotoxic chemotherapy in phase III randomized trials. Considering the findings regarding the excellent benefit and better safety profile of EGFR TKIs in EGFR mutation positive patients, these targeted therapeutic agents can be now considered as first-line treatment in this setting of patients. This review will discuss the new evidences in the role of EGFR-TKIs in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Mutação , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Descoberta de Drogas , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
20.
Curr Med Chem ; 18(33): 5022-32, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22050750

RESUMO

Angiogenesis is known to be essential for the development and progression of cancer. Vascular endothelial growth factor (VEGF) is a critical mediator in tumor angiogenesis for many solid malignancies, including breast cancer. Increased levels of VEGF have been associated with poor clinical outcomes, including reduced survival. VEGF has become an attractive target for cancer therapy in view of its pivotal role in angiogenesis. The primary approaches for inhibiting angiogenesis have focused on inhibiting the activity of VEGF, either by targeting the VEGF ligand itself with monoclonal antibodies (mAbs) or by interfering with the signaling events downstream of VEGF through the use of tyrosine kinase inhibitors (TKIs). Bevacizumab is a recombinant, humanized monoclonal IgG1, anti-VEGF antibody that has demonstrated significant clinical benefit in several solid tumors. Bevacizumab has been approved for use in combination with paclitaxel for the first line treatment of patients with metastatic breast cancer (MBC) based on the results of the randomized phase III E2100 trial in which it improves response rate and time to progress when administered with weekly paclitaxel until disease progression. Several trials to define the role of bevacizumab in different setting of disease and in combination with different chemotherapy regimens and targeted therapy in breast cancer patients are ongoing. Other small molecule inhibitors of VEGF tyrosine kinase activity (TKIs) such as sunitinib, vandetanib and sorafenib are being tested in MBC. This review will focus on bevacizumab and on the developements of the main antiangiogenic agents in the treatment of breast cancer.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Bevacizumab , Ensaios Clínicos como Assunto , Feminino , Humanos , Paclitaxel/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo
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