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1.
Clin Lung Cancer ; 21(2): 145-152, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31982356

RESUMO

BACKGROUND: Lung cancer mortality has been found to decrease significantly with low-dose (LD) computed tomographic (CT) screening among current or former smokers. However, such a screening program is not implemented in France. This study assessed the feasibility of a lung cancer screening program using LD CT scan in a French administrative territory. We report here the results of the first screening round. PATIENTS AND METHODS: DEP KP80 was a single-arm prospective study initiated in May 2016. Participants aged 55 to 74 years, current or former smokers of ≥ 30 pack-years, were recruited. An annual LD CT scan was scheduled. Our algorithms considered nodules < 5 mm as negative findings and nodules > 10 mm as positive; for intermediate nodules between 5 and 10 mm, 3-month CT scan with doubling time measurement was recommended. All general practitioners, pulmonologists, and radiologists from the Somme department were solicited to participate. Subjects were selected by general practitioners or pulmonologists who checked the inclusion criteria and prescribed the CT scan. RESULTS: Over a 2.5-year period, 1307 subjects were recruited. Screening was negative in 733 cases (77.2%), positive in 54 (5.7%), and indeterminate in 162 (17.1%). After the 3-month scans, 57 subjects screened positive: 26 patients exhibited 31 lung cancers (67.7% of stage 0 to I), of whom 76.9% underwent surgical resection, and 29 had no cancer (false-positive rate = 3.1%). The prevalence of lung cancer was 2.7%. CONCLUSION: This study demonstrated the feasibility of organized lung cancer screening using LD CT scan within a real-life context in the general population.

2.
Bull Cancer ; 104(7-8): 652-661, 2017.
Artigo em Francês | MEDLINE | ID: mdl-28688747

RESUMO

INTRODUCTION: The French Cancer Plan 2014-2019 stresses the importance of strengthening collaboration between all stakeholders involved in the fight against cancer, including cancer cooperative groups and intergroups. This survey aimed to describe the basics characteristics and clinical research activity among the Cancer Cooperative Groups (Groupes coopérateurs en oncologie). The second objective was to identify facilitators and barriers to their research activity. METHODS: A questionnaire was sent to all the clinicians involved in 2014 as investigators in a clinical trial sponsored by one of the ten members of the Cancer Cooperative Groups network. The questions were related to their profile, research activity and the infrastructure existing within their healthcare center to support clinical research and related compliance activities. RESULTS: In total, 366 investigators responded to our survey. The academic clinical trials sponsored by the Cancer Cooperative Groups represented an important part of the research activity of the investigators in France in 2014. These academic groups contributed to the opening of many research sites throughout all regions in France. Factors associated with a higher participation of investigators (more than 10 patients enrolled in a trial over a year) include the existing support of healthcare professionals (more than 2 clinical research associate (CRA) OR=11.16 [3.82-32.6] compared to none) and the practice of their research activity in a University Hospital Center (CHU) rather than a Hospital Center (CH) (OR=2.15 [1.20-3.83]). CONCLUSION: This study highlighted factors that can strengthen investigator clinical research activities and subsequently improve patient access to evidence-based new cancer therapies in France.


Assuntos
Pesquisa Biomédica/estatística & dados numéricos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Neoplasias/terapia , Pesquisadores/estatística & dados numéricos , Adulto , Idoso , Institutos de Câncer/estatística & dados numéricos , França , Acesso aos Serviços de Saúde , Hospitais Gerais/estatística & dados numéricos , Hospitais Privados/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Pesquisadores/provisão & distribução , Inquéritos e Questionários
3.
J Thorac Oncol ; 11(10): 1644-52, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27449803

RESUMO

A shift in mortality and morbidity has been observed in people living with human immunodeficiency virus (PLWHIV) from acquired immunodeficiency syndrome (AIDS) to non-AIDS diseases. Lung cancer has the highest incidence rates among all the non-AIDS-defining malignancies and is associated with mortality rates that exceed those of other cancers. Strategies to increase lung cancer survival in PLWHIV are needed. Lung cancer screening with chest LDCT has been shown to be efficient in the general population at risk. The objective of this review is to discuss lung cancer screening with chest computed tomography in PLWHIV. Lung cancer screening in PLWHIV is feasible. Whether PLWHIV could benefit from an age threshold for screening that is earlier than the minimum age of 55 years usually required in the general population still needs further investigation. Studies evaluating smoking cessation programs and how they could be articulated with lung cancer screening programs are also needed in PLWHIV.


Assuntos
Infecções por HIV/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Programas de Rastreamento/métodos , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade
4.
Eur Respir J ; 48(3): 861-72, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27338193

RESUMO

In the Intergroupe Francophone de Cancérologie Thoracique 0501 trial the carboplatin-paclitaxel chemotherapy increased toxicity (most frequent, decreased neutrophil count, asthenia). We longitudinally compared health-related quality of life (HRQoL) of the two treatment arms.In total, 451 patients aged 70-89 years with advanced non-small cell lung cancer (NSCLC) were randomly assigned to receive carboplatin plus paclitaxel or vinorelbine or gemcitabine. HRQoL was assessed by means of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire at baseline, week 6 and week 18.Using a five-point decrease as the minimal clinically important difference, patients treated with the chemotherapy doublet exhibited a significant longer time until definitive deterioration (TUDD) for two HRQoL dimensions: physical functioning (median TUDD: 2.04 for the doublet versus 1.71 months for monotherapy; log-rank p=0.01) and nausea and vomiting (median: not reached versus 4.83, respectively; log-rank p=0.046). Cox multivariate analysis revealed the carboplatin and paclitaxel arm to be independently associated with longer TUDD for these two HRQoL dimensions. In addition, TUDD didn't significantly differ between the two arms for all the other HRQoL dimensions.The chemotherapy doublet did not reduce TUDD in elderly patients with advanced NSCLC. Moreover, TUDD was prolonged for two HRQoL dimensions, namely physical functioning and nausea and vomiting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Fatores de Tempo , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina
5.
Lancet ; 387(10026): 1405-1414, 2016 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-26719230

RESUMO

BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove effective. We aimed to assess the effect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as first-line treatment of advanced malignant pleural mesothelioma. METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients aged 18-75 years with unresectable malignant pleural mesothelioma who had not received previous chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0-2, had no substantial cardiovascular comorbidity, were not amenable to curative surgery, had at least one evaluable (pleural effusion) or measurable (pleural tumour solid thickening) lesion with CT, and a life expectancy of >12 weeks from 73 hospitals in France. Exclusion criteria were presence of central nervous system metastases, use of antiaggregant treatments (aspirin ≥325 mg per day, clopidogrel, ticlopidine, or dipyridamole), anti-vitamin K drugs at a curative dose, treatment with low-molecular-weight heparin at a curative dose, and treatment with non-steroidal anti-inflammatory drugs. We randomly allocated patients (1:1; minimisation method used [random factor of 0·8]; patients stratified by histology [epithelioid vs sarcomatoid or mixed histology subtypes], performance status score [0-1 vs 2], study centre, or smoking status [never smokers vs smokers]) to receive intravenously 500 mg/m(2) pemetrexed plus 75 mg/m(2) cisplatin with (PCB) or without (PC) 15 mg/kg bevacizumab in 21 day cycles for up to six cycles, until progression or toxic effects. The primary outcome was overall survival (OS) in the intention-to treat population. Treatment was open label. This IFCT-GFPC-0701 trial is registered with ClinicalTrials.gov, number NCT00651456. FINDINGS: From Feb 13, 2008, to Jan 5, 2014, we randomly assigned 448 patients to treatment (223 [50%] to PCB and 225 [50%] to PC). OS was significantly longer with PCB (median 18·8 months [95% CI 15·9-22·6]) than with PC (16·1 months [14·0-17·9]; hazard ratio 0·77 [0·62-0·95]; p=0·0167). Overall, 158 (71%) of 222 patients given PCB and 139 (62%) of 224 patients given PC had grade 3-4 adverse events. We noted more grade 3 or higher hypertension (51 [23%] of 222 vs 0) and thrombotic events (13 [6%] of 222 vs 2 [1%] of 224) with PCB than with PC. INTERPRETATION: Addition of bevacizumab to pemetrexed plus cisplatin significantly improved OS in malignant pleural mesothelioma at the cost of expected manageable toxic effects, therefore it should be considered as a suitable treatment for the disease. FUNDING: Intergroupe Francophone de Cancérologie Thoracique (IFCT).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Pemetrexede/administração & dosagem , Neoplasias Pleurais/tratamento farmacológico , Idoso , Bevacizumab/efeitos adversos , Cisplatino/efeitos adversos , Creatinina/sangue , Feminino , Humanos , Hipertensão/epidemiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/mortalidade , Mesotelioma/patologia , Pessoa de Meia-Idade , Pemetrexede/efeitos adversos , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/patologia , Proteinúria/epidemiologia , Trombose/epidemiologia , Fator A de Crescimento do Endotélio Vascular/sangue
6.
Lancet ; 387(10026): 1415-1426, 2016 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-26777916

RESUMO

BACKGROUND: The molecular profiling of patients with advanced non-small-cell lung cancer (NSCLC) for known oncogenic drivers is recommended during routine care. Nationally, however, the feasibility and effects on outcomes of this policy are unknown. We aimed to assess the characteristics, molecular profiles, and clinical outcomes of patients who were screened during a 1-year period by a nationwide programme funded by the French National Cancer Institute. METHODS: This study included patients with advanced NSCLC, who were routinely screened for EGFR mutations, ALK rearrangements, as well as HER2 (ERBB2), KRAS, BRAF, and PIK3CA mutations by 28 certified regional genetics centres in France. Patients were assessed consecutively during a 1-year period from April, 2012, to April, 2013. We measured the frequency of molecular alterations in the six routinely screened genes, the turnaround time in obtaining molecular results, and patients' clinical outcomes. This study is registered with ClinicalTrials.gov, number NCT01700582. FINDINGS: 18,679 molecular analyses of 17,664 patients with NSCLC were done (of patients with known data, median age was 64·5 years [range 18-98], 65% were men, 81% were smokers or former smokers, and 76% had adenocarcinoma). The median interval between the initiation of analysis and provision of the written report was 11 days (IQR 7-16). A genetic alteration was recorded in about 50% of the analyses; EGFR mutations were reported in 1947 (11%) of 17,706 analyses for which data were available, HER2 mutations in 98 (1%) of 11,723, KRAS mutations in 4894 (29%) of 17,001, BRAF mutations in 262 (2%) of 13,906, and PIK3CA mutations in 252 (2%) of 10,678; ALK rearrangements were reported in 388 (5%) of 8134 analyses. The median duration of follow-up at the time of analysis was 24·9 months (95% CI 24·8-25·0). The presence of a genetic alteration affected first-line treatment for 4176 (51%) of 8147 patients and was associated with a significant improvement in the proportion of patients achieving an overall response in first-line treatment (37% [95% CI 34·7-38·2] for presence of a genetic alteration vs 33% [29·5-35·6] for absence of a genetic alteration; p=0·03) and in second-line treatment (17% [15·0-18·8] vs 9% [6·7-11·9]; p<0·0001). Presence of a genetic alteration was also associated with improved first-line progression-free survival (10·0 months [95% CI 9·2-10·7] vs 7·1 months [6·1-7·9]; p<0·0001) and overall survival (16·5 months [15·0-18·3] vs 11·8 months [10·1-13·5]; p<0·0001) compared with absence of a genetic alteration. INTERPRETATION: Routine nationwide molecular profiling of patients with advanced NSCLC is feasible. The frequency of genetic alterations, acceptable turnaround times in obtaining analysis results, and the clinical advantage provided by detection of a genetic alteration suggest that this policy provides a clinical benefit. FUNDING: French National Cancer Institute (INCa).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Classe I de Fosfatidilinositol 3-Quinases , Receptores ErbB/genética , Feminino , França/epidemiologia , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Fosfatidilinositol 3-Quinases/genética , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptores Proteína Tirosina Quinases/genética , Receptor ErbB-2/genética , Adulto Jovem
7.
Bull Cancer ; 103(1): 66-72, 2016 Jan.
Artigo em Francês | MEDLINE | ID: mdl-26682626

RESUMO

The phase III trials of adjuvant and neoadjuvant chemotherapy showed a 5 % increase survival but the clinical research in this area is difficult because the duration of the trials with overall survival as primary end point is around 10years. To shorten the duration of these studies, the use of surrogate end points such as disease-free survival or relapse-free survival is possible, but does not significantly reduce the duration of studies. Several studies in and outside the lung cancer showed histological complete response or the percentage of viable tumor cells after chemotherapy could be correlated with survival and thus become an interesting alternative criterion. If this is verified, clinical studies of preoperative chemotherapy should be shortened which would allow patients faster access to innovative treatment in the perioperative situation.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Terapia Neoadjuvante , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Quimioterapia de Indução , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia , Cuidados Pré-Operatórios , Editoração , Neoplasias Retais/tratamento farmacológico , Fatores de Tempo
8.
Eur J Cancer ; 52: 120-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26682871

RESUMO

BACKGROUND: We investigated whether the health-related quality of life (HRQoL) score is a prognostic factor for overall survival (OS) in elderly patients with advanced non-small-cell lung cancer (NSCLC). METHODS: We included 451 NSCLC patients aged 70-89 years enrolled in the Intergroupe Francophone de Cancérologie Thoracique 0501 trial, using scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at baseline to investigate the prognostic value of HRQoL for OS, in addition to conventional factors. Cox regression model was used for both univariate and multivariate analyses of OS. RESULTS: Global health status (GH) dimension score at baseline was associated with favourable OS when adjusted for clinical, functional, and histological factors (hazard ratio [HR]: 0.986; 95% confidence interval [CI]: 0.980-0.992). We distinguished three groups according to GH score: high (GH <46), intermediate (46 ≤ GH ≤ 67), and low (GH >67) mortality risk. The median OS values were 14.5, 8.2, and 5.3 months in the low-, intermediate-, and high-risk categories, respectively (log-rank P <0.0001). In the high-risk group, doublet chemotherapy was not associated with favourable OS (HR: 0.70; 95% CI: 0.49-1.003; P=0.052), whereas in the intermediate- and low-risk groups, doublet chemotherapy was associated with favourable OS (HR: 0.72; 95% CI: 0.54-0.96; P=0.023 and HR: 0.50; 95% CI: 0.30-0.84; P=0.0089, respectively). CONCLUSION: This study supports the additional prognostic value of HRQoL data at diagnosis to identify vulnerable subpopulations in elderly NSCLC patients. HRQoL could thus be valuable in selecting patients who will benefit from doublet chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/psicologia , Neoplasias Pulmonares/psicologia , Qualidade de Vida , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Técnicas de Apoio para a Decisão , Feminino , França/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Modelos Lineares , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Análise Multivariada , Estadiamento de Neoplasias , Seleção de Pacientes , Modelos de Riscos Proporcionais , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
9.
J Geriatr Oncol ; 6(3): 233-40, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25698450

RESUMO

OBJECTIVES: We evaluated the impact of age in a randomized phase II trial that compared three first-line drugs in elderly patients with advanced non-small cell lung cancer (NSCLC) and a poor performance status (PS). MATERIALS AND METHODS: Patients with advanced NSCLC with a PS of 2 or 3 were enrolled into a multicenter randomized trial: arm A, gefitinib; arm B, gemcitabine; and arm C, docetaxel. We performed subgroup analyses according to age. RESULTS: Between December 2004 and June 2007, 127 patients were enrolled. Analyses were performed between the two subgroups aged <70years (younger, n=56) and ≥70years (older, n=71). Patients mainly had adenocarcinoma (46% young vs. 51%: elderly), of which 62% vs. 75% had a PS of 2, respectively. Significantly more elderly patients were women and non-smokers, and there was a non-significant trend towards more PS-2 among the elderly. Progression-free survival (PFS) was 1.4months (95% CI: 1.1-1.9) for younger compared to 2.3months (95% CI: 2.1-2.9) for elderly patients. Overall survival (OS) was 2.0months (95% CI: 1.5-2.4) and 3.7months (95% CI: 2.4-4.8), respectively. Toxicity did not differ between younger and older patients. NSCLC was better controlled in elderly patients after three cycles of monotherapy compared to younger patients (p=0.034). When adjusted for stratification criteria, age was the main prognostic factor for PFS. Adjusted HRs for PFS was 0.57 (95% CI: 0.38-0.85) for the elderly compared to patients aged <70years (p=0.004). CONCLUSIONS: Older patients had a decreased risk of progression/death compared to younger patients. Single-agent chemotherapy can be considered for patients aged ≥70years with a PS of 2.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Docetaxel , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Quinazolinas/uso terapêutico , Taxa de Sobrevida , Taxoides/uso terapêutico , Resultado do Tratamento
10.
J Thorac Oncol ; 10(3): 420-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25514806

RESUMO

INTRODUCTION: To evaluate the perception of lung cancer in the general population to identify obstacles in patient-doctor communications. METHODS: A prospective nationwide survey was conducted using a questionnaire and lexical approaches given to 2200 healthy subjects selected within a representative polling database. RESULTS: Of the 1469 subjects eligible for full analysis, most were well informed regarding the epidemiological changes to lung cancer and the main risk factors. The overall survival of patients with lung cancer (32%) was overestimated, and the survival of patients with early stages of lung cancer was underestimated (52%). Lung cancer was identified as a severe disease (82%) with a worse prognosis than other cancers. Most of the population was aware of the main treatments available, except for targeted therapy. Using lexical analyses, we observed that a major proportion considered lung cancer to be a tobacco-induced, life-threatening disease that involved major treatment, and a minor proportion considered it to be an environmentally induced disease. Compared with breast cancer, lung cancer was characterized by a greater feeling of guilt and was more frequently associated with lifestyle. CONCLUSIONS: We have identified knowledge gaps in the perception of lung cancer and have highlighted a need for a public information campaign on lung-cancer screening to promote the good survival rate from early-stage disease and the progress achieved with new therapeutic strategies.


Assuntos
Atitude Frente a Saúde , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/psicologia , Percepção , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Feminino , França/epidemiologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/prevenção & controle , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
12.
Eur Respir J ; 43(1): 240-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24114964

RESUMO

There is no dedicated study on second-line treatment for elderly patients with advanced nonsmall cell lung cancer (NSCLC). We report the results on second-line erlotinib therapy from our previously published phase III study comparing single-agent therapy with platinum-based doublet (carboplatin plus paclitaxel) therapy in 451 elderly patients. Erlotinib was given to patients exhibiting disease progression or experiencing excessive toxicity during first-line therapy, until further progression or unacceptable toxicity. In total, 292 (64.7%) patients received erlotinib as second-line therapy. Initial performance status 0-1, stage IV NSCLC and an Activities of Daily Living score of 6 were independent factors for receiving erlotinib. Median (95% CI) overall survival was 4 (3.2-6.7) versus 6.8 (5.0-8.3) months in the single-agent and doublet arms, respectively (p=0.089). Performance status 0-1, never having smoked, adenocarcinoma and weight loss ≤5% were favourable independent prognostic factors of survival, whereas the randomisation arm had no significant impact. Among the 292 patients who received erlotinib, 60 (20.5%) experienced grade 3-4 toxic effects, the most frequent being rash. Erlotinib as second-line therapy is feasible, leading to efficacy results similar to those obtained in a previous randomised study that was not dedicated to elderly patients, with acceptable toxicity.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Progressão da Doença , Cloridrato de Erlotinib , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Falha de Tratamento , Resultado do Tratamento
14.
Eur J Cancer ; 49(12): 2654-64, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23735703

RESUMO

HYPOTHESIS: There will be a detectable increase in overall survival (OS) using preoperative (PRE) as opposed to perioperative (PERI) chemotherapy in resectable StageI-II non-small-cell lung cancer (NSCLC). METHODS: This multicenter, open-label, randomised trial with a 2×2 factorial design first compared two chemotherapy strategies (PRE versus PERI), then two chemotherapy regimens (gemcitabine-cisplatin [GP] versus paclitaxel-carboplatin [TC]). The PRE group received two preoperative cycles followed by two additional preoperative cycles, while the PERI group underwent two preoperative cycles followed by two postoperative cycles, the 3rd and 4th cycles being given only to responders in both cases. RESULTS: A total of 528 patients were randomised, 267 of which were assigned to the PRE group and 261 to the PERI group. Three-year OS did not differ between the two groups (67.4% and 67.7%, respectively; hazard ratio (HR)=1.01 [0.79-1.30], p=0.92), nor did 3-year disease-free survival, response rates, toxicity, or postoperative mortality. Pathological complete response was observed in 22 (8.2%) and 16 patients (6.1%), respectively. Although quality of life did not differ significantly, chemotherapy compliance was significantly higher in the PRE group. The proportion of responders who received Cycles 3 and 4 was significantly higher in the PRE group (90.4% versus 75.2%, p=0.001). In responders, the dose intensity of Cycles 3 and 4 was higher in the PRE group than in the PERI group (mean relative dose intensity of 90.4% versus 82.6%, respectively; p=0.0007). There was no difference between GP and TC in 3-year OS (HR=0.97 [95% confidence interval (CI): 0.76-1.25], p=0.80) or response rates. However, the regimens' toxicity profiles differed. CONCLUSIONS: This study failed to demonstrate any difference in survival between patients receiving preoperative and perioperative chemotherapy in early-stage NSCLC. The increase from two to four preoperative chemotherapy cycles did not increase the pathological response rate.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Assistência Perioperatória , Cuidados Pré-Operatórios , Qualidade de Vida , Resultado do Tratamento , Vômito/induzido quimicamente
15.
Bull Cancer ; 99(11): 1039-44, 2012 Nov.
Artigo em Francês | MEDLINE | ID: mdl-23137673

RESUMO

Lung cancer is a common and serious disease, only early stage are curable. It is a logical candidate for a screening policy, especially as current and former smokers are easy to identify. The inefficiency of the chest radiograph is now proven, while the low-dose CT has shown promising data following a recent randomized study in North America. Yet, this is not specific and find a great number of benign anomalies. These limitations must be well known to physicians, radiologists and chest physicians if they use the individual screening.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Tomografia Computadorizada Espiral/métodos , Diagnóstico Diferencial , Humanos , Doses de Radiação , Ensaios Clínicos Controlados Aleatórios como Assunto , Fumar/efeitos adversos
16.
J Clin Oncol ; 30(28): 3516-24, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22949150

RESUMO

PURPOSE: This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. PATIENTS AND METHODS: Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS). RESULTS: PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P < .001) and erlotinib (median, 2.9 v 1.9 months; HR, 0.69; 95% CI, 0.54 to 0.88; log-rank P = .003) versus observation; this benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. CONCLUSION: Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Quimioterapia de Indução , Neoplasias Pulmonares/tratamento farmacológico , Quimioterapia de Manutenção , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/administração & dosagem , Adulto , Idoso , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinazolinas/uso terapêutico
17.
J Thorac Oncol ; 7(5): 841-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22722786

RESUMO

INTRODUCTION: Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non-small-cell lung cancer (NSCLC) after neoadjuvant chemotherapy resulted in improved outcome, and to determine predictive factors for pCR. METHODS: Eligible patients with stage-IB or -II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique phase-III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen. RESULTS: Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival was 80.0% compared with 55.8% in the non-pCR group (p = 0.0007). In multivariate analyses, pCR was a favorable prognostic factor of overall survival (relative risk = 0.34; 95% confidence interval = 0.18-0.64) in addition to squamous-cell carcinoma, weight loss less than or equal to 5%, and stage-IB disease. Five-year disease-free survival was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p < 0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (odds ratio [OR] = 4.30; 95% confidence interval = 1.90-9.72). CONCLUSION: Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in stage-IB-II NSCLC. Our study is the largest published series evaluating pCRs after preoperative chemotherapy. The only factor predictive of pCR was squamous-cell carcinoma. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Terapia Neoadjuvante , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Ifosfamida/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Taxa de Sobrevida
18.
Eur J Cancer ; 48(9): 1299-311, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22464348

RESUMO

An estimated 10-25% of lung cancers worldwide occur in never smokers, i.e. individuals having smoked less than 100 cigarettes in their lifetime. Lung cancer in never smokers (LCINS) is more frequent in women, although large geographic variations are found. Histologically, adenocarcinomas predominate. The mere existence of LCINS suggests that risk factors other than smoking must be present. Exposure to environmental tobacco smoke (particularly in women) and exposure to workplace carcinogens (particularly in men) are the two most important alternative risk factors. However, a history of either is absent in more than a third of LCINS. The large proportion of women in LCINS suggest a hormonal element that may interact with other identified factors such as hereditary risks, a history of respiratory infections or disease, exposure to air pollution, cooking and heating fumes, or exposure to ionising radiation. The study of genomic polymorphisms finds constitutive DNA variations across subjects according to their smoking status, particularly in genes coding for enzymes that participate in the metabolism of certain carcinogens, in those coding for DNA repair enzymes, or in genes associated with tobacco addiction, or inflammatory processes. The type of molecular mutation in p53 or KRAS varies with smoking status. EGFR mutations are more frequent in never smokers, as are EML4-ALK fusions. The mutually exclusive nature of certain mutations is a strong argument in favour of separate genetic paths to cancer for ever smokers and never smokers. In the present paper we review current clinical and molecular aspects of LCINS.


Assuntos
Neoplasias Pulmonares/epidemiologia , Fumar/epidemiologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/genética , Adenocarcinoma de Pulmão , Humanos , Neoplasias Pulmonares/genética , Mutação , Polimorfismo Genético , Fatores de Risco
19.
Clin Cancer Res ; 18(10): 2976-86, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22434665

RESUMO

PURPOSE: To evaluate prognostic and predictive molecular biomarkers in early-stage non-small cell lung carcinoma (NSCLC) receiving neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: The IFCT-0002 trial compared two neoadjuvant regimens in 528 stages I to II NSCLC patients. DNA extraction of snap-frozen surgical samples taken from 208 patients receiving gemcitabine-cisplatin or paclitaxel-carboplatin regimens allowed for the identification of 3p allelic imbalance, Ras association domain family 1A (RASSF1A) and death-associated protein kinase 1 (DAPK1) promoter methylation, and epidermal growth factor receptor, K-ras, and TP53 mutations. Multivariate analysis identified prognostic and predictive effects of molecular alterations. A Bootstrapping approach was used to assess stability of the prognostic models generating optimism corrected indexes. RESULTS: RASSF1A methylation correlated significantly with shorter disease-free survival (DFS; adjusted HR = 1.88, 95% CI: 1.25-2.82, P = 0.0048) and shorter median overall survival (OS; adjusted HR = 2.01, 95% CI: 1.26-3.20, P = 0.020). A computed bootstrap resampling strategy led to a prognostic model, including RASSF1A, DAPK1, and tumor stage, dividing patients into three prognostic groups, with median OS ranging from 34 months for high-risk patients (HR for death = 3.85, 95% CI: 1.79-6.40) to more than 84 months for moderate (HR = 1.85, 95% CI: 0.97-3.52) and low-risk patients (reference group; P = 0.00044). In addition, RASSF1A methylation predicted longer DFS in patients treated with paclitaxel-carboplatin compared with gemcitabine-cisplatin (adjusted HR = 0.47, 95% CI: 0.23-0.97, P(interaction) = 0.042). CONCLUSIONS: Following neoadjuvant chemotherapy, RASSF1A methylation negatively impacted prognosis of early-stage NSCLC. Along with DAPK1 methylation and tumor stage, RASSF1A methylation allowed definition of three subgroups with strikingly different prognosis. Conversely, significantly longer DFS following paclitaxel-based neoadjuvant chemotherapy for patients whose tumors showed RASSF1A methylation suggested its predictive interest in stages I and II NSCLC.


Assuntos
Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Metilação de DNA , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas Reguladoras de Apoptose/genética , Biomarcadores Tumorais/genética , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Citoesqueleto/genética , Citoesqueleto/metabolismo , Proteínas Quinases Associadas com Morte Celular , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Genes p53 , Genes ras , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Prognóstico , Regiões Promotoras Genéticas , Interferência de RNA , RNA Interferente Pequeno , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/genética
20.
Bull Cancer ; 99(4): E43-8, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22450449

RESUMO

BACKGROUND: Cisplatin is a pivotal drug in combined chemotherapy for non-small cell and small-cell lung cancers (NSCLC or SCLC), but its renal toxicity limits its use. Current guidelines recommend 24 h hydration: thus hospitalization is required. The aim of this retrospective study was to confirm the safety of short hydration before giving an intermediate-to-high dose of cisplatin in an outpatient clinic. PATIENTS AND METHODS: Patients eligible had NSCLC or SCLC and were being treated with a chemotherapy regimen that included cisplatin ≥ 75 mg/m(2). They were given the same short hydration protocol for 1 day. Nephrotoxicity was defined as ≥ grade 1 according to NCIC common toxicity criteria. Predictive factors for nephrotoxicity were analyzed. RESULTS: Three hundred and fifty-seven consecutive patients (median age 58 years, range: 25-81) were reviewed. Twenty-one patients (6%) had ≥ grade 1 nephrotoxicity and all except one had grade 1 toxicity according to NCIC criteria for common toxicity (SC < 1,5 N). Predictive factors independently associated with nephrotoxicity included associated co-morbid conditions (hypertension, diabetes, heart disease) (OR = 4.97 CI 95% [1.8-13.7] P = 0.002), initial serum creatinine ≥ 100 µmol/L (OR = 8.3 CI 95% [2.55-27.4] P = 0.0005), and dose cycle of cisplatin ≥ 100 mg/m(2) (OR = 10.8 CI 95% [3.6-32.5] P < 0.0001). CONCLUSION: Rapid outpatient administration of a single dose of cisplatin at ≥ 75 mg/m(2) is feasible without a high risk of nephrotoxicity.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Hidratação/métodos , Nefropatias/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/efeitos adversos , Creatinina/metabolismo , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Etoposídeo/administração & dosagem , Feminino , Humanos , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxoides/administração & dosagem , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina
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