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To respond to the legitimate questions raised by the application of invasive methods of monitoring and life-support techniques in cancer patients admitted in the ICU, the European Lung Cancer Working Party and the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique, set up a consensus conference. The methodology involved a systematic literature review, experts' opinion and a final consensus conference about nine predefined questions1. Which triage criteria, in terms of complications and considering the underlying neoplastic disease and possible therapeutic limitations, should be used to guide admission of cancer patient to intensive care units?2. Which ventilatory support [High Flow Oxygenation, Non-invasive Ventilation (NIV), Invasive Mechanical Ventilation (IMV), Extra-Corporeal Membrane Oxygenation (ECMO)] should be used, for which complications and in which environment?3. Which support should be used for extra-renal purification, in which conditions and environment?4. Which haemodynamic support should be used, for which complications, and in which environment?5. Which benefit of cardiopulmonary resuscitation in cancer patients and for which complications?6. Which intensive monitoring in the context of oncologic treatment (surgery, anti-cancer treatment )?7. What specific considerations should be taken into account in the intensive care unit?8. Based on which criteria, in terms of benefit and complications and taking into account the neoplastic disease, patients hospitalized in an intensive care unit (or equivalent) should receive cellular elements derived from the blood (red blood cells, white blood cells and platelets)?9. Which training is required for critical care doctors in charge of cancer patients?
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Estado Terminal , Neoplasias , Bélgica , Cuidados Críticos , Humanos , Unidades de Terapia Intensiva , Neoplasias/terapia , Respiração Artificial , Revisões Sistemáticas como AssuntoRESUMO
Thymic tumours are rare diseases that for most of the cases are cured with surgery and eventually adjuvant radiotherapy. However, about 30% of patients present with advanced stage or relapsing tumours, which require administration of chemotherapy. While cisplatin-adriamycin-cyclophosphamide combination is regularly prescribed, other drugs have been assessed in the literature. Our aim is to evaluate the effectiveness (response rate) of systemic treatments, whatever the therapeutic line, including chemotherapy, targeted therapies and immunotherapies, in thymoma and thymic carcinoma, using the principles of evidence-based medicine. A systematic review was designed using the PICO system, by an experienced librarian and clinicians' experts in thoracic oncology, through the Ovid Medline system. Only phase II-IV trials and retrospective studies including at least 14 patients treated with the same regimen were considered. Articles were independently selected by at least two investigators. Fifty-five eligible articles were retrieved. Sixty% were dealing with platinum-based regimens, mainly cisplatin, and showed overall similar activity (mostly response rate above 50%) independently of the line of treatment or histological type (thymoma versus thymic carcinoma). Non-platinum based regimens included octreotide-prednisone and capecitabine-gemcitabine. Promising data of immunotherapy with antiPDL1 antibody (pembrolizumab) requires confirmation. Based on available data, the most popular and active regimens are cisplatin-anthracycline (CAP or ADOC) or cisplatin-etoposide combinations that should be recommended when considering first-line chemotherapy in thymoma or thymic carcinoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Timoma/tratamento farmacológico , Neoplasias do Timo/tratamento farmacológico , Antraciclinas/administração & dosagem , Cisplatino/administração & dosagem , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Análise de Sobrevida , Timoma/patologia , Neoplasias do Timo/patologiaRESUMO
OBJECTIVES: To assess if induction radiochemotherapy followed by consolidation chemotherapy (arm A) will improve survival in comparison with the same chemotherapy given as induction followed by consolidation concurrent radiochemotherapy (arm B) in patients with unresectable non-metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy consisted in a combination of cisplatin with docetaxel, with one initial course for each patient, two courses in single modality therapy and weekly administration during chest irradiation (66â¯Gy). RESULTS: A total of 125 patients were randomised before early closure of the study because of poor accrual and an unplanned blind interim analysis which suggested that the continuation of the study would have been futile. Mature survival results showed no significant difference between both modalities with median survival times, respectively in arms A and B, of 19.6 months and 18.3 months, two years survival rates of 44% and 44% and five years survival rates of 23% and 26%. Toxicity was acceptable. CONCLUSIONS: Our randomised study did not demonstrate survival difference between induction concurrent radiochemotherapy followed by consolidation chemotherapy and induction chemotherapy followed by consolidation concurrent radiochemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Quimioterapia de Consolidação/métodos , Docetaxel/uso terapêutico , Quimioterapia de Indução/métodos , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimiorradioterapia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de SobrevidaRESUMO
INTRODUCTION: In a literature meta-analysis, we showed survival benefits for regimens including cisplatin [hazard ratio (HR) 0.61; 95% confidence interval (CI), 0.57-0.66] and for those including etoposide (HR 0.65; 0.61-0.69). That benefit was mainly observed when etoposide alone or in combination with cisplatin was included in the chemotherapy regimens. Our objective was to determine if chemotherapy with both drugs improves survival in comparison to a non-platinum regimen with etoposide. METHODS: Extensive small-cell lung cancer patients were randomized between cisplatin-etoposide (CE) and ifosfamide + etoposide + epirubicin regimen (IVE) between 2000 and 2013. RESULTS: 176 and 170 eligible patients were allocated to CE and IVE (315 deaths were required before analysis), respectively. Objective response rates were not significantly different: 60% with CE and 59% with IVE. No statistically significant difference in median survival and 1-year and 2-year was observed with rates of 9.6 months, 31 and 5% for CE and 10 months, 39 and 9% for IVE, respectively. HR was 0.84 (95% CI 0.68-1.05, p = 0.16). Only two prognostic factors for survival were retained in multivariate analysis: sex with HR = 0.69 (95% CI 0.49-0.97, p = 0.03) and performance status with HR = 0.53 (95% CI 0.49-0.97, p < 0.0001). After adjustment for these prognostic factors, HR for survival was 0.83 (95% CI 0.65-1.08, p = 0.17). There was more thrombopenia in the CE regimen and more leukopenia with IVE. CONCLUSION: Combination of CE failed to improve survival in comparison to an etoposide-containing regimen without cisplatin. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00658580?term=ELCWP+01994&rank=1, identifier NCT00658580.
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The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes that can complicate lung cancer appears useful. This article is the fourth of a series of five and deals mainly with neurological paraneoplastic syndromes involving the peripheral nervous system and the neuromuscular junction and muscles.
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Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/epidemiologia , Síndromes Paraneoplásicas/complicações , Síndromes Paraneoplásicas/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Autoimunidade , Humanos , Músculos/imunologia , Músculos/patologia , Junção Neuromuscular/imunologia , Junção Neuromuscular/patologia , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/terapia , Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Sistema Nervoso Periférico/imunologia , Sistema Nervoso Periférico/patologiaRESUMO
The development of new immune treatment in oncology and particularly for lung cancer may induce new complications, particularly activation or reactivation of auto-immune diseases. In this context, a systematic review on the auto-immune paraneoplastic syndromes that can complicate lung cancer appears useful. This article is the last of a series of five and deals mainly with onconeural antibodies involved in neurological paraneoplastic syndromes and provides the final discussion.
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Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/epidemiologia , Síndromes Paraneoplásicas/complicações , Síndromes Paraneoplásicas/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Autoimunidade , Humanos , Músculos/imunologia , Músculos/patologia , Junção Neuromuscular/imunologia , Junção Neuromuscular/patologia , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/terapia , Síndromes Paraneoplásicas do Sistema Nervoso/complicações , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Sistema Nervoso Periférico/imunologia , Sistema Nervoso Periférico/patologiaRESUMO
(18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) complements conventional imaging for diagnosing and staging lung cancer. Two literature-based meta-analyses suggest that maximum standardised uptake value (SUVmax) on PET has univariate prognostic value in nonsmall cell lung cancer (NSCLC). We analysed individual data pooled from 12 studies to assess the independent prognostic value of binary SUVmax for overall survival.After searching the published literature and identifying unpublished data, study coordinators were contacted and requested to provide data on individual patients. Cox regression models stratified for study were used.Data were collected for 1526 patients (median age 64â years, 60% male, 34% squamous cell carcinoma, 47% adenocarcinoma, 58% stage I-II). The combined univariate hazard ratio for SUVmax was 1.43 (95% CI 1.22-1.66) and nearly identical if the SUV threshold was calculated stratifying for histology. Multivariate analysis of patients with stage I-III disease identified age, stage, tumour size and receipt of surgery as independent prognostic factors; adding SUV (HR 1.58, 95% CI 1.27-1.96) improved the model significantly. The only detected interaction was between SUV and stage IV disease.SUV seems to have independent prognostic value in stage I-III NSCLC, for squamous cell carcinoma and for adenocarcinoma.
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Adenocarcinoma/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos , Carga TumoralRESUMO
PURPOSE: We aimed to assess computed tomography (CT) intratumoral heterogeneity changes, and compared the prognostic ability of the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an alternate response method (Crabb), and CT heterogeneity in non-small cell lung cancer treated with chemotherapy with and without bevacizumab. MATERIALS AND METHODS: Forty patients treated with chemotherapy (group C) or chemotherapy and bevacizumab (group BC) underwent contrast-enhanced CT at baseline and after 1, 3, and 6 cycles of chemotherapy. Radiologic response was assessed using RECIST 1.1 and an alternate method. CT heterogeneity analysis generating global and locoregional parameters depicting tumor image spatial intensity characteristics was performed. Heterogeneity parameters between the 2 groups were compared using the Mann-Whitney U test. Associations between heterogeneity parameters and radiologic response with overall survival were assessed using Cox regression. RESULTS: Global and locoregional heterogeneity parameters changed with treatment, with increased tumor heterogeneity in group BC. Entropy [group C: median -0.2% (interquartile range -2.2, 1.7) vs. group BC: 0.7% (-0.7, 3.5), P=0.10] and busyness [-27.7% (-62.2, -5.0) vs. -11.5% (-29.1, 92.4), P=0.10] showed a greater reduction in group C, whereas uniformity [1.9% (-8.0, 9.8) vs. -5.0% (-13.9, 5.6), P=0.10] showed a relative increase after 1 cycle but did not reach statistical significance. Two (9%) and 1 (6%) additional responders were identified using the alternate method compared with RECIST in group C and group BC, respectively. Heterogeneity parameters were not significant prognostic factors. CONCLUSIONS: The alternate response method described by Crabb identified more responders compared with RECIST. However, both criteria and baseline imaging heterogeneity parameters were not prognostic of survival.
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Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Meios de Contraste , Feminino , Humanos , Iohexol/análogos & derivados , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Critérios de Avaliação de Resposta em Tumores Sólidos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Vorinostat is a histone deacetylase inhibitor that changes gene expression and protein activity. On the basis of the clinical benefit reported in patients with malignant pleural mesothelioma treated in a phase 1 study of vorinostat, we designed this phase 3 trial to investigate whether vorinostat given as a second-line or third-line therapy improved patients' overall survival. METHODS: This double-blind, randomised, placebo-controlled trial was done in 90 international centres. Patients with measurable advanced malignant pleural mesothelioma and disease progression after one or two previous systemic regimens were eligible. After stratification for Karnofsky performance status, histology, and number of previous chemotherapy regimens, patients were randomly assigned (1:1) by use of an interactive voice response system with a block size of four to either treatment with vorinostat or placebo. Patients received oral vorinostat 300 mg (or matching placebo) twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 of a 21-day cycle. The primary endpoints were overall survival and safety and tolerability of vorinostat. The primary efficacy comparison was done in the intention-to-treat population, and safety and tolerability was assessed in the treated population. This trial is registered with ClinicalTrials.gov, number NCT00128102. FINDINGS: From July 12, 2005, to Feb 14, 2011, 661 patients were enrolled and randomly assigned to receive either vorinostat (n=329) or placebo (n=332) and included in the intention-to-treat analysis. Median overall survival for vorinostat was 30·7 weeks (95% CI 26·7-36·1) versus 27·1 weeks (23·1-31·9) for placebo (hazard ratio 0·98, 95% CI 0·83-1·17, p=0·86). The most common grade 3 or worse adverse events for patients treated with vorinostat were fatigue or malaise (51 [16%] patients in the vorinostat group vs 25 [8%] in the placebo group]) and dyspnoea (35 [11%] vs 45 [14%]). INTERPRETATION: In this randomised trial, vorinostat given as a second-line or third-line therapy did not improve overall survival and cannot be recommended as a therapy for patients with advanced malignant pleural mesothelioma. FUNDING: Merck & Co.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ácidos Hidroxâmicos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Ácidos Hidroxâmicos/efeitos adversos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Mesotelioma Maligno , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Placebos , VorinostatRESUMO
Salvage chemotherapy (CT) for relapsing or refractory small cell lung cancer (SCLC) remains disappointing. In vitro experiments showed that valproic acid increases apoptosis of SCLC cell lines exposed to doxorubicin, vindesine and bis(2-chloroethyl)amine. The primary objective of this phase II study was to determine whether epigenetic modulation with valproic acid in addition to a doxorubicin, vindesine and cyclophosphamide (VAC) regimen improves 6-month progression-free survival (PFS). Patients with pathologically proven SCLC refractory to prior platinum derivatives and etoposide were eligible. After central registration, patients received VAC plus daily oral valproic acid. 64 patients were registered, of whom six were ineligible. Seven patients did not receive any CT, leaving 51 patients assessable for the primary end-point. The objective response rate was 19.6%. Median PFS was 2.8â months (95% CI 2.5-3.6â months) and 6-month PFS was 6%. Median survival time was 5.9â months (95% CI 4.7-7.5â months). Toxicity was mainly haematological, with 88% and 26% grade 3-4 neutropenia and thrombopenia, respectively. Despite an interesting response rate, the addition of valproic acid to VAC did not translate into adequate PFS in relapsing SCLC or SCLC refractory to platinum-etoposide.
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The use of noninferiority randomised trials for patients with advanced non-small cell lung cancer has emerged during the past 10-15â years but has raised some issues related to their justification and methodology. The present systematic review aimed to assess trial characteristics and methodological aspects. All randomised clinical trials with a hypothesis of noninferiority/equivalence, published in English, were identified. Several readers extracted a priori defined methodological information. A qualitative analysis was then performed. We identified 20 randomised clinical trials (three phase II and 17 phase III), 11 of them being conducted in strong collaboration with industry. We highlighted some deficiencies in the reports like the lack of justification for both the noninferiority assumption and the definition of the noninferiority margin, as well as inconsistencies between the results and the authors' conclusions. CONSORT guidelines were better followed for general items than for specific items (p<0.001). Improvement in the reporting of the meth"odology of noninferiority/equivalence trials is needed to avoid misleading interpretation and to allow readers to be fully aware of the assumptions underlying the trial designs. They should be restricted to limited specific situations with a strong justification why a noninferiority hypothesis is acceptable.
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Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Algoritmos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Oncologia/métodos , Reprodutibilidade dos Testes , Projetos de Pesquisa , RiscoRESUMO
We have shown previously that the pro-inflammatory cytokine TNF (tumour necrosis factor) could drive sLe(x) (sialyl-Lewis(x)) biosynthesis through the up-regulation of the BX transcript isoform of the ST3GAL4 (ST3 ß-galactoside α-2,3-sialyltransferase 4) sialyltransferase gene in lung epithelial cells and human bronchial mucosa. In the present study, we show that the TNF-induced up-regulation of the ST3GAL4 BX transcript is mediated by MSK1/2 (mitogen- and stress-activated kinase 1/2) through the ERK (extracellular-signal-regulated kinase) and p38 MAPK (mitogen-activated protein kinase) pathways, and increases sLe(x) expression on high-molecular-mass glycoproteins in inflamed airway epithelium. We also show that the TNF-induced sLe(x) expression increases the adhesion of the Pseudomonas aeruginosa PAO1 and PAK strains to lung epithelial cells in a FliD-dependent manner. These results suggest that ERK and p38 MAPK, and the downstream kinase MSK1/2, should be considered as potential targets to hamper inflammation, bronchial mucin glycosylation changes and P. aeruginosa binding in the lung of patients suffering from lung diseases such as chronic bronchitis or cystic fibrosis.
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Aderência Bacteriana/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Proteínas Quinases S6 Ribossômicas 90-kDa/fisiologia , Sialiltransferases/genética , Fator de Necrose Tumoral alfa/farmacologia , Proteínas de Bactérias/fisiologia , Brônquios/efeitos dos fármacos , Brônquios/enzimologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Oligossacarídeos/fisiologia , Pseudomonas aeruginosa/fisiologia , Mucosa Respiratória/metabolismo , Antígeno Sialil Lewis X , Sialiltransferases/metabolismo , Células Tumorais Cultivadas , Regulação para Cima/efeitos dos fármacos , beta-Galactosídeo alfa-2,3-SialiltransferaseRESUMO
AIM: Cisplatin doublets are standard 1st line treatment for advanced non-small cell lung cancer (NSCLC), without accurate predictor for response and survival, but important toxicity. Our aims were to identify predictive (for response) and prognostic (for survival) biological signatures in patients with NSCLC using messenger RNAs (mRNA) and miRNA expression. METHODS: Patients with pathologically proven untreated NSCLC, receiving 1st line cisplatin-vinorelbine and with an assessable lesion were eligible. A bronchial biopsy was lysed into Tripure Isolation Reagent on ice, snap frozen, and stored at -80°C. mRNA expression was analyzed using microarrays Agilent Technologies. miRNA expression was assessed using TaqMan Low Density Arrays (756 human miR panel, Applied Biosystems). Validation was performed by RT-PCR on the selected genes. Survival was measured from the registration date and response assessed by WHO criteria. RESULTS: Biopsies for transcriptomic analyses were obtained from 60 consecutive patients. No statistically significant differences were observed according to the main clinical characteristics, response rate (43 vs. 41%) or survival (median 25 vs. 29 months) between derivation and validation sets. In the derivation set (n = 38 patients), two mRNA and one miRNA predictive signatures for response were obtained. One mRNA and one miRNA prognostic signatures were derived from the first set, allowing an adequate distinction of patients with good and poor overall and progression-free survivals. None of these signatures could be validated in the validation set (n = 22 patients). CONCLUSION: In this prospective study with advanced NSCLC treated with cisplatin-vinorelbine, we were able to derive with high throughput techniques predictive and prognostic signatures based on transcriptomic analyses. However, these results could not be reproduced in an independent validation set. The role of miRNA and mRNA as predictive or prognostic factors remains a research topic and the use of high throughput technology in that context questionable. The ClinicalTrials.gov study identifier is NCT00864266 (www.clinicaltrials.gov).
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AIM: While meta-analyses and clinical trials show improved survival in advanced NSCLC treated with platinum-containing chemotherapy, there are few data concerning front-line platinum-free ifosfamide-based regimens. We aimed to compare cisplatin-based chemotherapy to ifosfamide-gemcitabine (IG) with pre-defined second-line docetaxel. PATIENTS AND METHODS: 693 Untreated advanced inoperable NSCLC cases were randomised to either GIP (gemcitabine, ifosfamide, cisplatin), DP (docetaxel, cisplatin) or IG. Primary outcome was overall survival. RESULTS: Median age of the patients was 58 years with a predominance of males (75%), adenocarcinoma (56%), Karnofsky PS 80-100 (77%) and stage-IV disease (81%). Median survival times were 8.7, 8.8 and 8.3 months for IG, GIP and DP (p=0.79). GIP presented with (p<0.05) greater neutropenia, thrombopenia, vomiting, while greater cardiotoxicity, diarrhea, peripheral neuropathy were observed for DP and encephalopathy for IG. CONCLUSION: In advanced NSCLC, cisplatin-based CT is not superior to a platinum-free regimen (ifosfamide-gemcitabine) with a favourable toxicity profile.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Ifosfamida/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Análise de SobrevidaRESUMO
OBJECTIVES: To determine whether CT can depict early perfusion changes in lung cancer treated by anti-angiogenic drugs, allowing prediction of response. METHODS: Patients with non-small cell lung cancer, treated by conventional chemotherapy with (Group 1; n = 17) or without (Group 2; n = 23) anti-vascular endothelial growth factor (anti-VEGF) drug (bevacizumab) underwent CT perfusion before (TIME 0) and after 1 (TIME 1), 3 (TIME 2) and 6 (TIME 3) cycles of chemotherapy. The CT parameters evaluated included: (1) total tumour vascular volume (TVV) and total tumour extravascular flow (TEF); (2) RECIST (Response Evaluation Criteria in Solid Tumours) measurements. Tumour response was also assessed on the basis of the clinicians' overall evaluation. RESULTS: In Group 1, significant reduction in perfusion was identified between baseline and: (1) TIME 1 (TVV, P = 0.0395; TEF, P = 0.015); (2) TIME 2 (TVV, P = 0.0043; TEF, P < 0.0001); (3) TIME 3 (TVV, P = 0.0034; TEF, P = 0.0005) without any significant change in Group 2. In Group 1: (1) the reduction in TVV at TIME 1 was significantly higher in responders versus non-responders at TIME 2 according to RECIST (P = 0.0128) and overall clinicians' evaluation (P = 0.0079); (2) all responders at TIME 2 had a concurrent decrease in TVV and TEF at TIME 1. CONCLUSION: Perfusion CT demonstrates early changes in lung cancer vascularity under anti-angiogenic chemotherapy that may help predict therapeutic response. KEY POINTS: ⢠Perfusion CT has the potential of providing in vivo information about tumour vasculature. ⢠CT depicts early and specific perfusion changes in NSCLC under anti-angiogenic drugs. ⢠Specific therapeutic effects of anti-angiogenic drugs can be detected before tumour shrinkage. ⢠Early perfusion changes can help predict therapeutic response to anti-angiogenic treatment. ⢠Perfusion CT could be a non-invasive tool to monitor anti-angiogenic treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Bevacizumab , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Perfusão , Estudos Prospectivos , Interpretação de Imagem Radiográfica Assistida por Computador , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
BACKGROUND: The importance of clinical predictors in the treatment of non-small-cell lung cancer (NSCLC) has increased during the last decade. This retrospective study analyzed the combined patient-level data from two phase II trials that investigated the efficacy and safety of combination chemotherapy with vinorelbine and mitomycin in patients with locally advanced or metastatic NSCLC. The aim of this analysis was to determine if patients' baseline and disease characteristics, including histology, gender, smoking history, and expression of TTF-1, might be potential predictors of outcome. METHODS: Response rates, unadjusted survival times, and Cox covariate-adjusted hazard ratios (HRs) were calculated. Results were reported separately for each subgroup in each individual trial and in the pooled data set. RESULTS: A total of 175 patients were included in this analysis. Adjusted HRs for both overall survival (OS) and progression free survival (PFS) favored the nonadenocarcinoma histology subgroup, achieving a statistical significance for OS in the pooled data (n = 175; HR 0.68; 95 % CI 0.49-0.94; p = 0.019). TTF-1-negative immunohistochemistry was associated with a significantly higher response rate (25 vs. 0 %; p = 0.04) and with a nonsignificant advantage in OS (n = 33; HR 1.23; 95 % CI 0.56-2.73; p = 0.608). Gender and smoking history were not strongly related to outcome. CONCLUSIONS: The results of this analysis indicate that patients with nonadenocarcinoma histology might get superior benefit from combination chemotherapy with vinorelbine and mitomycin. These results should be confirmed in a prospective study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/química , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Ensaios Clínicos Fase II como Assunto , Proteínas de Ligação a DNA/análise , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/química , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Seleção de Pacientes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Fatores de Transcrição , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
There are no international guidelines for an appropriate and cost-effective follow-up for resected nonsmall cell lung cancer (NSCLC). We retrospectively reviewed the outcome of NSCLC patients after curative surgery. Follow-up included physical examination and chest radiography every 3 months, and chest computed tomography (CT) scan, bronchoscopy, abdominal ultrasound, brain CT scan and bone scan every 6 months for 3 years, then every year over the following 2 years. Prognostic factors and costs were analysed. Median overall survival following surgery for NSCLC in 162 patients was 38.5 months. Recurrence occurred in 85 (52.5%) patients including 41 (48%) symptomatic subjects. Disease-free survival was similar between patients with asymptomatic recurrence versus symptomatic patients (11.4 versus 12 months; p=0.41). Recurrence was detected by physical examination or chest radiography in 47 (55.3%) patients. Curative-intent therapy was provided in 18 (41%) out of 44 patients with asymptomatic recurrence and in four (10%) out of 41 symptomatic cases (p=0.001). Median overall survival from time of recurrence was higher in asymptomatic patients than in symptomatic patients (15.5 versus 7.2 months; p=0.001). The cost per year of life gained was USD32 700 (22 397). An extensive follow-up, with acceptable cost, may improve the outcome of patients with resected NSCLC through detection of asymptomatic recurrences; however, validation by prospective studies is required.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Broncoscopia , Carcinoma Pulmonar de Células não Pequenas/economia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Análise Custo-Benefício , Intervalo Livre de Doença , Feminino , Seguimentos , Custos de Cuidados de Saúde , Humanos , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Radiografia Torácica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , UltrassonografiaRESUMO
BACKGROUND: Combination of bevacizumab and weekly paclitaxel showed synergitic effects, anti-tumor efficacy and a good toxicity profile for patients with breast cancer but has never been evaluated in non small cell lung cancer (NSCLC). We retrospectively reviewed safety and efficacy of this regimen in metastatic non-squamous NSCLC as fourth-line therapy or beyond. METHODS: Patients were identified from a prospective database. Treatment consisted in paclitaxel 80 mg/m(2) on days 1, 8 and 15 and bevacizumab 15 mg/kg on day 1, every 3 weeks until progression or unacceptable toxicity. RESULTS: Twenty patients were included in this study. Objective response rate at first evaluation was 40% (8/20), confirmed response rate was 15% (3/20) and disease control rate was 75% (15/20). The median progression-free survival and overall survival were 6.4 months (CI95% 4.1-9) and 9.6 months (CI95% 7-19.7). Grade 3-4 adverse events included neutropenia (4/20), onycholysis (2/20) and infection (2/20). One patient died from a bowel perforation and another one died from unknown cause. Prolonged responses were observed in a patient who had received bevacizumab as part of first-line chemotherapy and in another one who harbored an ALK rearrangement. CONCLUSIONS: In our experience, combination of bevacizumab and weekly paclitaxel exhibited acceptable toxicity and had encouraging anti-tumor efficacy as fourth-line treatment or beyond for non-squamous NSCLC patients, supporting further evaluation in larger prospective studies.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Paclitaxel/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Estudos ProspectivosRESUMO
Numerous lung cell lines are currently used as in vitro models for pharmacological and toxicological studies. However, no exhaustive report about the metabolic capacities of these models in comparison with those of lung tissues is available. In the present study, we used a high-throughput quantitative real-time reverse transcription-polymerase chain reaction strategy to characterize the expression profiles of 380 genes encoding proteins involved in the metabolism and disposition of xenobiotics in 10 commonly used lung cell lines (A549, H292, H358, H460, H727, Calu-1, 16HBE, 1 HAEO, BEAS-2B, and L-132) and four primary cultures of human bronchial epithelial cells. Expression results were then compared with those previously obtained in human nontumoral and tumoral lung tissues. Our results revealed disparities in gene expression between lung cell lines or when comparing lung cell lines with primary cells or lung tissues. Primary cell cultures displayed the highest similarities with bronchial mucosa in terms of transcript profiling and therefore seem to be the most relevant in vitro model for investigating the metabolism and bioactivation of toxicants and drugs in bronchial epithelium. H292 and BEAS-2B cell lines, which exhibited the highest homology in gene expression pattern with primary cells and the lowest number of dysregulated genes compared with nontumoral lung tissues, could be used as surrogates for toxicological and pharmacological studies. Overall, our study should provide references for researchers to choose the most appropriate in vitro model for analyzing the cellular effects of drugs or airborne toxicants on the airway.