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1.
Arch Pediatr ; 29(8): 554-559, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36210238

RESUMO

BACKGROUND: In pediatric intensive care units (PICUs), parents and healthcare professionals attend to children who verbally and non-verbally express their pain and suffering, fears, anxieties, desires, and wishes in complex intensive care situations. What can we learn from these experiences to improve the way we can take care of and support children? OBJECTIVES: The main objective of this clinical ethics study was to focus on the experience stories of parents during their child's hospitalization in a PICU, to analyze their discourse, and to propose an ethical perspective. METHOD: The current research collects the experience reports of parents during their child's hospitalization in a PICU and those of the caregivers who treated them. A total of 17 semi-directive interviews were conducted in the PICU of the Nantes University Hospital from November 2017 to June 2019. Each interview lasted around 1 h. The main results of our study are analyzed and informed by the four ethical principles of T. Beauchamp and J. Childress: autonomy, beneficence, non-maleficence, and justice. RESULTS: The interviews highlighted the difficulties encountered by parents during the hospitalization of their children, such as the distance between their home and the hospital, the technicality of PICU environment, and the difficulty in finding their place as parents. For medical and paramedical teams, their main concerns are undoubtedly to improve the coherence and continuity of their stand toward parents, to promote parental autonomy, and to remain fully aware of the profound existential changes that the child's illness brings about for parents: It is the caregivers' duty to take this into account and to respect the parents' rhythm as much as possible. CONCLUSIONS: The main disagreements between healthcare teams and parents, where they exist, are communication problems that are easily controlled, for the most part, by caregivers.


Assuntos
Cuidadores , Unidades de Terapia Intensiva Pediátrica , Criança , Humanos , Pais , Pesquisa Qualitativa , Pessoal de Saúde
3.
Ann Oncol ; 16(1): 81-9, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15598943

RESUMO

BACKGROUND: This phase II trial compared docetaxel-cisplatin (DC) with vinorelbine-cisplatin (VC), both as first-line therapy followed by cross-over at progression to single-agent vinorelbine or docetaxel in advanced non-small-cell lung cancer (NSCLC). METHODS: Overall, 115 patients received DC (docetaxel 75 mg/m(2) and cisplatin 100 mg/m(2) both on day 1, every 3 weeks, arm A1) and 118 VC (vinorelbine 30 mg/m(2)/week on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, arm B1) for six cycles, and subsequently maintained by monotherapy with docetaxel (A1) or vinorelbine (B1) with cross-over on disease progression to vinorelbine 30 mg/m(2) days 1 and 8 (A2), or docetaxel 100 mg/m(2), day 1, both every 3 weeks (B2). The primary end point was overall response rate (ORR). RESULTS: Patient characteristics were balanced; median follow-up was 8.8 months. First-line response rate was 33.9% with DC and 26.3% with VC (P=0.20). In arms A1 and B1, respectively: duration of response was similar (8.2 versus 8.4 months); median time to progression was 5 months in both; median survival was 8 versus 9 months (P=0.38); 1-, 2- and 3-year survival was 36% versus 35%, 17% versus 10% and 13% versus 6% (P not significant). However, with a low number of long-term survivors, statistical significance was not reached. Overall, almost half of the patients crossed over to second-line therapy; there were no response with vinorelbine and 6 (11.2%) partial responses with docetaxel. Considering the safety profile, the occurrence of febrile neutropenia was 9.6% with DC and 26.3% with VC. Treatment-related mortality was 2.5% with DC and 8.5% with VC. CONCLUSIONS: The trend in favour of the DC arm in ORR, even though statistical significance was not reached, is consistent with previous reports. This study suggests an activity of first-line DC in advanced NSCLC, and that second-line vinorelbine does not provide additional clinical benefit. As already shown in other studies, the use of DC in first-line should provide a better percentage of long-term survivors, despite the absence of efficacy of the second-line in our study.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Taxoides/uso terapêutico , Vimblastina/análogos & derivados , Vimblastina/uso terapêutico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Estudos Cross-Over , Progressão da Doença , Docetaxel , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Análise de Sobrevida , Taxoides/administração & dosagem , Vimblastina/administração & dosagem , Vinorelbina
4.
Ann Oncol ; 12(1): 59-67, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11249050

RESUMO

PURPOSE: To determine if the timing of whole brain radiotherapy (WBRT) with respect to chemotherapy with cisplatin and vinorelbine would influence survival in patients with non-small-cell lung cancer (NSCLC) and concurrent brain metastasis. PATIENTS AND METHODS: One hundred seventy-six patients with brain metastasis from NSCLC were included in the study between July 1995 and October 1997. All patients received chemotherapy with cisplatin 100 mg/m2 on day 1 and vinorelbine 30 mg/m2 on days 1, 8, 15, 22. Cycles were repeated every four weeks. Evaluation of response was performed after two, four or six cycles. After two cycles, chemotherapy was administered to the responders to a maximum of six cycles. Patients were randomised to receive WBRT 30 Gy/10 fx/12 days and delayed corticosteroids. (arm A) for the intracranial nonresponders, or early on day 1 to 12 during the first cycle of chemotherapy (arm B). RESULTS: One hundred seventy-one patients were eligible: eighty-six in arm A and eighty-five in arm B; none had received prior chemotherapy; seventy-six and seventy-three, respectively, were assessable for response. There was a 21% overall objective response rate (OR) (with 1 complete response and 17 partial responses) after two cycles of chemotherapy alone (arm A) and a 20% OR (with 17 partial responses) to chemotherapy and early WBRT (arm B). The intracranial OR was 27% and 33%, respectively (P = 0.12). The six months survival rate (46% and 40%) and the median survival duration (24 and 21 weeks, respectively) were not significantly different between the two arms (P = 0.83, log-rank test). The major toxicity was severe or life-threatening neutropenia (grade 4), which occurred in 35% of arm A patients and 36% of arm B patients. There were thirteen treatment-related deaths (six in arm A and seven in arm B). There was no difference between the arms for haematological and neuro-toxicities. CONCLUSIONS: These results confirm the efficacy of chemotherapy in brain metastases of NSCLC and suggest that the timing (early or delayed) of WBRT did not influence survival of NSCLC with brain metastasis treated with concurrent chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Vimblastina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Fracionamento da Dose de Radiação , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vimblastina/administração & dosagem , Vinorelbina
5.
Acta Oncol ; 39(4): 501-8, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11041113

RESUMO

We report the results of three consecutive programs combining initial intensive chemotherapy and radiotherapy in the treatment of patients with limited small-cell lung cancer (SCLC). The objective was to test the feasibility and the effect of high-dose chemotherapy and three thoracic irradiation programs on survival and patterns of relapse. Forty-two patients with limited SCLC were enrolled. All patients received high-dose chemotherapy (vindesine, etoposide, doxorubicin, cisplatin and cyclophosphamide or ifosfamide). In the SC 84 program, chest and brain radiotherapy was delivered during each course of chemotherapy, with a complementary irradiation after chemotherapy. In the SC 86 and SC 92 programs, patients received chemotherapy followed by thoracic irradiation and prophylactic brain and spinal axis radiotherapy. At the end of treatment, 40 patients (95%) were in complete response. During chemotherapy, high levels of toxicity were noted. All patients had grade IV hematological toxicities. The extra-hematological toxicities were digestive (grade III: 21%; grade IV: 7%) and hepatic (grades III and IV: 14%). During irradiation, patients presented digestive, pulmonary and hematological toxicities. Five patients developed late toxicities and a second malignancy was observed in 4 patients. The 2- and 5-year survival rates for all patients were 51% and 27%, respectively. Despite the marked toxicity of the initial intensive chemotherapy, the treatments are tolerable and effective in the control of extra-thoracic micrometastases, whereas they are less effective for thoracic primary tumor.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Antineoplásicos/efeitos adversos , Cisplatino/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Ifosfamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Análise de Sobrevida , Resultado do Tratamento , Vindesina/administração & dosagem
6.
Lung Cancer ; 29(3): 205-16, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10996423

RESUMO

The purpose of this study was to evaluate the efficacy and safety of docetaxel as first- and second-line chemotherapy for advanced non-small cell lung cancer (NSCLC) under routine clinical conditions. Two hundred and three patients with advanced NSCLC received docetaxel 100 mg/m2 (1-h intravenous infusion) every 3 weeks, with oral corticosteroid pre-medication, of whom 173 were eligible. Median age was 60 (29-78) years and median Karnofsky performance status was 80% (60-100). A total of 77% of patients had metastatic disease, 33% had bone metastases and 18% had liver metastases. The treatment was second-line or more for 72 patients (35%). Overall response rates in the eligible population were 19.7% [95% CI, 12.5-23.0] for both treatments, 22.6% for first-line treatment and 13.8% for second-line treatment. Median survival was 8.3 months and 1-year survival was 35% for the overall population (8.7 months and 38%, respectively, for patients receiving first-line treatment and 7.2 months and 27%, respectively, for patients receiving second-line treatment). Neutropenia, grade 3 and 4, occurred in 57% of the cycles and 5% of patients experienced febrile neutropenia. Alopecia (62% of patients), neuro-sensory symptoms (32%), asthenia (28%), diarrhea (22%), nausea (22%) and nail disorders (20%) were the most common non-hematological adverse effects. A total of 33% of patients suffered fluid retention, despite the use of corticosteroid pre-medication, but this was only severe in 1.5% of patients. It was possible to confirm the efficacy of docetaxel as a single agent for first- and second-line chemotherapy in a large patient population treated in a community setting.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Docetaxel , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento
7.
Cancer ; 89(3): 523-33, 2000 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-10931451

RESUMO

BACKGROUND: The purposes of this study were to identify prognostic factors for response to chemotherapy, overall survival, and long term survival of patients with small cell lung carcinoma and to construct a classification of patients on the basis of their expected overall survival. METHODS: In the 763 patients registered in 4 consecutive clinical trials conducted by the European Lung Cancer Working Party from 1982 to 1993, the impact of 21 pretreatment variables assessable in a routine practice was analyzed for the various outcomes with a minimum follow-up of 5 years. RESULTS: The key prognostic role of disease extent was confirmed for all the outcomes. Additional independent prognostic factors for response to chemotherapy were gender, neutrophil count, and hemoglobin level; for overall survival, these factors were Karnofsky performance status, gender, and neutrophil count. Recursive partitioning and amalgamation algorithms (RECPAM) analysis classified patients into 4 groups, taking into consideration disease extent, Karnofsky performance status, age, gender, and neutrophil count. Median survival times for the 4 groups were 60, 47, 36, and 28 weeks, respectively. For long term survival, defined as a minimum survival of 2 years (9% of the patients), Karnofsky performance status was the only independent predictive factor, along with the achievement of a complete response (if this was taken into consideration). Small cell lung carcinoma remained the main cause of death among these patients. Cure was infrequent, with only 14 patients alive and disease free at 5 years (1.8%). CONCLUSIONS: In this study the long term prognosis associated with small cell lung carcinoma was poor. The well-known prognostic values of disease extent and Karnofsky performance status were confirmed, but the authors also identified age and gender (which are more controversial) as independent characteristics, in addition to citing the role of complete response in the attainment of long term survival. The independent role of neutrophils observed by the authors. must be validated by further studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Carcinoma de Células Pequenas/mortalidade , Ensaios Clínicos como Assunto , Feminino , Seguimentos , Humanos , Modelos Logísticos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida
8.
Eur Respir J ; 12(5): 1228-9, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9864025

RESUMO

A 75-yr-old male hospitalized for vascular purpura with joint pain had a medical history of polymyalgia rheumatica. A generalized oedematous syndrome occurred and the patient also presented with haemoptysis and complained of transient paraesthesia of the hands and feet. Renal biopsy showed lesions of focal segmental proliferative glomerulonephritis associated with a few cellular crescents. Lung biopsy showed small-cell neuroendocrine carcinoma. After the first course of chemotherapy signs of vasculitis disappeared. Small-cell neuroendocrine carcinomas, which represent 25% of all lung cancers, have numerous paraneoplastic (especially neurological) extrapulmonary manifestations. Disseminated vasculitis has never been described with this type of cancer, whereas nonsmall-cell carcinomas are associated essentially with cutaneous vasculitis or purpura rheumatica. In the case reported here, anticancer chemotherapy allowed vasculitic manifestations to be treated.


Assuntos
Carcinoma Neuroendócrino/complicações , Carcinoma de Células Pequenas/complicações , Neoplasias Pulmonares/complicações , Síndromes Paraneoplásicas , Vasculite/complicações , Idoso , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Síndromes Paraneoplásicas/patologia , Vasculite/patologia
10.
Anticancer Res ; 18(1A): 193-200, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9568077

RESUMO

Non-small-cell lung carcinoma (NSCLC) is a particularly serious disease because of its chemoresistance to current treatments. To investigate the nature of his generally innate resistance, we cloned an established cell line (NSCLC-N6) derived from a non-small cell bronchopulmonary carcinoma. Four cell subpopulations (C15, C65, C92 and C98) were isolated from the mother line. These four clones were studied in comparison with each other for cell doubling time in vitro, ploidy, chemosensitivity in vitro, cytogenetic, expression of the oncogene erb-B2 and other tumor markers (Kr, CEA and Chr A). Each clone shows a distinct biologic pattern for various biological parameters. Our results indicated hat cell doubling time (in vitro) increased when the hyperploid population was prevailing. The clones differ in their chemosensitivity to therapeutic agents. This cellular diversity might help to explain why these tumors are chemoresistant. This heterogeneity within NSCLC tumors should be taken into consideration in the choice of treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Aneuploidia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cromogranina A , Cromograninas/metabolismo , Aberrações Cromossômicas/patologia , Transtornos Cromossômicos , Células Clonais , DNA de Neoplasias/metabolismo , Humanos , Cariotipagem , Queratinas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Receptor ErbB-2/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacos
11.
Eur J Cancer ; 33(14): 2326-32, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9616276

RESUMO

The aim of this study was the assessment of the predictive value for survival of an antitumoral response to three courses of chemotherapy in association with various pretreatment characteristics in patients with non-resectable non-small cell lung cancer treated by cisplatin- (or carboplatin)-based combination regimens. Patients considered for this study were eligible patients with advanced non-small cell lung cancer registered in one of the seven trials conducted by the European Lung Cancer Working Party from December 1980 to August 1991. All these trials tested chemotherapy regimens with platinum derivatives (cisplatin and/or carboplatin). In this population of 1052 eligible patients, 752 were assessed in this analysis. Data were prospectively collected on 23 pretherapeutic variables and objective response after three chemotherapy cycles. The predictive value of response to chemotherapy on survival (measured from the time of response assessment i.e. 12 weeks after registration in the trial) was studied by univariate analysis as well as by multivariate methods (adjustment of the impact of several covariates simultaneously on the dependent variable) with adjustment for the pretreatment prognostic variables. After three cycles of chemotherapy, the global estimated median survival time was 24 weeks with a 95% confidence interval of 22-25 weeks. By univariate analysis, we identified an objective response to chemotherapy as a highly significant discriminant marker (P < 0.0001) for further survival with estimated median survival times of 41 weeks (95% CI: 38-46) and 19 weeks (95% CI: 17-20), respectively, for the responding and non-responding patients. In a Cox regression model fitted to the data using a forward stepwise procedure, this variable was the first selected explanatory variable. Its effect was adjusted by the introduction in the model of initial disease extent, Karnofsky performance status, serum calcium level and white blood cell count. These results were consistent with those obtained by application of recursive partitioning and amalgamation algorithms (RECPAM) which led to a classification of the patients into three homogeneous subgroups. Our results, using a classical Cox regression model consistent with those highlighted by application of a RECPAM analysis, found an objective response to chemotherapy to be a predominant predictive factor for further survival, although it did not allow any conclusion about a causal relationship. The RECPAM results led to a classification of the patients into three subgroups which needs to be validated in other series.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Cisplatino/administração & dosagem , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Feminino , Previsões , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
12.
Rev Mal Respir ; 14(6): 445-9, 1997 Dec.
Artigo em Francês | MEDLINE | ID: mdl-9496602

RESUMO

The European Lung Cancer Working Party has investigated prognostic factors for response, overall survival, long term survival in a population with advanced non small cell lung cancer registered in a clinical trial evaluating platinum derivatives-containing chemotherapy regimens. Various factors have been identified in multivariate analyses and were classified using RECPAM methodology. In addition to the clinical factors such as disease extent and performance status were shown, as significant predictors, rarely studied biological factors like pretherapeutic leucocyte and polynuclear levels. The obtention of an objective response to chemotherapy appeared to be a major prognostic factor for further survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Fatores Etários , Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Ensaios Clínicos como Assunto , Feminino , Previsões , Humanos , Avaliação de Estado de Karnofsky , Contagem de Leucócitos , Neoplasias Pulmonares/patologia , Masculino , Estudos Multicêntricos como Assunto , Análise Multivariada , Estadiamento de Neoplasias , Neutrófilos/patologia , Prognóstico , Sistema de Registros , Indução de Remissão , Fatores Sexuais , Taxa de Sobrevida , Resultado do Tratamento
13.
Anticancer Res ; 17(6D): 4595-8, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9494574

RESUMO

The correlation between the degree of expression of the multidrug resistance-1 (MDR-1) gene and the process of differentiation into non-small-cell, bronchopulmonary carcinoma was studied in vitro and in vivo. For this purpose, a technique for the quantitative analysis of MDR-1 gene expression was developed by competitive reverse-transcriptase polymerase chain reaction. The study of 9 epidermoid carcinomas with various degrees of differentiation did not enable us to establish a correlation in vivo in the patient. However, an in vitro study performed on a non-small-cell lung carcinoma cell line and two of its clones showed that MDR-1 gene expression increased with the degree of differentiation, which was confirmed in vivo when this line was xenografted into nude mice.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistência a Múltiplos Medicamentos , Neoplasias Pulmonares/patologia , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Diferenciação Celular , Humanos , Cinética , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Nus , Reação em Cadeia da Polimerase , Transplante Heterólogo , Células Tumorais Cultivadas , Microglobulina beta-2/biossíntese
14.
Lung Cancer ; 16(1): 21-33, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9017582

RESUMO

PURPOSE: To identify pretreatment variables predicting response to platinum derivatives containing chemotherapy in patients with unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients included in one of the 7 consecutive clinical trials conducted by the European Lung Cancer Working Party between December 1980 and August 1991. All patients received a cisplatin or carboplatin containing chemotherapy. We analyzed 22 potential prognostic factors including sex, age, histology, performance status, weight loss, type of lesions, extent of disease, main metastatic sites and several biological parameters, namely white blood cell count (WBC), neutrophil count, platelet count, hemoglobinemia, creatininemia, serum alkaline phosphatases and LDH. RESULTS: On 1052 eligible patients. 107 were not assessable for response. The objective response rate was 26% (95% C.I.: 23, 29%). Univariate analysis identified as statistically significantly associated with a higher objective antitumoral response rate the following characteristics: a normal platelet count, the absence of skin metastasis, the absence of adrenal metastasis, a higher creatininemia, a normal hemoglobinemia, an older age and a normal WBC count. On a restricted set of variables including data from 777 patients, a multivariate logistic regression model disclosed age and platelet count as significantly and independently related to response rate. CONCLUSION: Clinical and demographic characteristics of patients with unresectable NSCLC, as well as routine laboratory parameters, could not accurately predict response to chemotherapy in a population of patients selected for a clinical trial. Future studies on this subject should include more sophisticated variables as new biomolecular makers.


Assuntos
Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento
15.
Semin Oncol ; 23(5 Suppl 10): 43-7, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8893881

RESUMO

Sixty-six patients with advanced non-small cell lung cancer have been entered into a phase I/II study of a combination of gemcitabine and cisplatin. An initial phase I portion of the study has been completed, and 16 patients have been entered using a fixed dose of gemcitabine 1,000 mg/m2 as a 30-minute intravenous infusion weekly for 3 weeks. Cisplatin was administered on day 15 following gemcitabine with appropriate prehydration and posthydration. The study was designed to allow for sequential groups of three patients to receive three dose levels of cisplatin (60 mg/m2, 75 mg/ m2, and 100 mg/m2). Dose modification and patient numbers were to be increased at any dose level if significant toxicity was observed. The regimen was well tolerated at all doses, and the final level of cisplatin 100 mg/m2 was expanded to 10 patients before the phase II portion was opened. Neutropenia (World Health Organization grade 4 in three patients) and thrombocytopenia (grade 3 or 4 in five patients) were the main hematologic toxicities recorded. These episodes were brief and uncomplicated. Grade 3 nausea and vomiting occurred in 12 patients, but was no worse than would be expected from cisplatin alone. Alopecia, when it occurred, was minimal (no hair loss in 10 patients and grade 1 or 2 in six patients). No significant renal toxicity or neurotoxicity was seen. A phase II study with cisplatin 100 mg/m2 and gemcitabine 1,000 mg/m2 has been opened, and to date 43 patients are evaluable for response. Eighteen (42%) patients have achieved partial remissions. The study will close when 50 evaluable patients have been entered.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adolescente , Adulto , Idoso , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gencitabina
16.
Anticancer Res ; 16(3A): 1209-12, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8702238

RESUMO

We studied the pharmacomodulating effects of a marine substance, bistramide D, which is capable of inducing terminal differentiation on the expression of the c-erb-B1, ras, src, myc and p53 genes in the NSCLC-N6 cell line established from a non-small cell lung carcinoma. Analysis (subsequent to treatment) demonstrated that among the genes for which it was possible to detect expression, namely c-erb-B1, c-myc and p53, only the expression of the p53 gene varied significantly. The increase of the expression rate of the p53 gene underlines its prominent role in the control of cell proliferation and differentiation.


Assuntos
Neoplasias Brônquicas/metabolismo , Neoplasias Brônquicas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteína Supressora de Tumor p53/biossíntese , Antineoplásicos/farmacologia , Northern Blotting , Neoplasias Brônquicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Receptores ErbB/biossíntese , Receptores ErbB/genética , Éteres Cíclicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes p53 , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Oncogenes , Proteínas Proto-Oncogênicas c-myc/biossíntese , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas pp60(c-src)/biossíntese , Proteínas Proto-Oncogênicas pp60(c-src)/genética , RNA Neoplásico/análise , RNA Neoplásico/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Proteínas ras/biossíntese , Proteínas ras/genética
17.
Anticancer Drugs ; 6 Suppl 6: 33-7, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8718423

RESUMO

Collaborative phase I and II studies of the combination of gemcitabine and cisplatin in patients with advanced non-small cell lung cancer are ongoing at five centres in the UK and France. In the initial completed phase I study, 16 patients (15 evaluable) have been entered using a fixed dose of gemcitabine 1000 mg/m2 given as a 30 min intravenous infusion weekly for 3 weeks. On the third week the gemcitabine was immediately followed by cisplatin with pre- and post-hydration. This regimen required only 1 night of hospitalization every 4 weeks. The study design was for sequential groups of patients to receive 3 dose levels of cisplatin (60 mg/m2, 75 mg/m2 and 100 mg/m2) but these doses would be modified and the number of patients at any dose level could be increased if significant toxicity was observed. Three patients were to be entered at the first two dose levels and 10 patients were to confirm the maximum tolerated dose (if reached) or expand the database on toxicity at the final predetermined dose level. The major haematological toxicities were neutropenia (grade 4 in 3 patients) and thrombocytopenia (grade 3 or 4 in 5 patients) but both were of short duration and uncomplicated. Grade 3 nausea and vomiting occurred in 12 patients but was no worse than would be expected from cisplatin alone. Alopecia was not a problem (no hair loss in 10 patients and grade 1 or 2 in 6 patients) and no significant renal or neurotoxicity was seen. A phase II study using cisplatin 100 mg/m2 in combination with gemcitabine 1000 mg/m2 has been opened and to date 19 patients are evaluable for response. Eight (42%) have achieved partial remissions. The study is ongoing and will recruit 50 evaluable patients.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Gencitabina
18.
J Clin Oncol ; 13(5): 1221-30, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7738625

RESUMO

PURPOSE: This study attempted to determine the prognostic value for survival of various pretreatment characteristics in patients with nonresectable non-small-cell lung cancer in the context of more than 10 years of experience of a European Cooperative Group. PATIENTS AND METHODS: We included in the analysis all eligible patients (N = 1,052) with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working Party (ELCWP) during one decade. The patients were treated by chemotherapy regimens based on platinum derivatives. We prospectively collected 23 variables and analyzed them by univariate and multivariate methods. RESULTS: The global estimated median survival time was 29 weeks, with a 95% confidence interval of 27 to 30 weeks. After univariate analysis, we applied two multivariate statistical techniques. In a Cox regression model, the selected explanatory variables were disease extent, Karnofsky performance status, WBC and neutrophil counts, metastatic involvement of skin, serum calcium level, age, and sex. These results were confirmed by application of recursive partitioning and amalgamation algorithms (RECPAM), which led to classification of the patients into four homogeneous subgroups. CONCLUSION: We confirmed by our analysis the role of well-known independent prognostic factors for survival, but also identified the effect of the neutrophil count, rarely studied, with the use of two methods: a classical Cox regression model and a RECPAM analysis. The classification of patients into the four subgroups we obtained needs to be validated in other series.


Assuntos
Algoritmos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Análise de Variância , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Contagem de Células Sanguíneas , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Feminino , Humanos , Avaliação de Estado de Karnofsky , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Redução de Peso
19.
Rev Mal Respir ; 12(4): 353-7, 1995.
Artigo em Francês | MEDLINE | ID: mdl-7481047

RESUMO

The aim of this study was to estimate the evolution of the incidence of mesothelioma in the Loire-Atlantique department since 1956 and to register all the cases diagnosed between 1985 and 1992 and to complete the data of earlier studies carried out between 1956 and 1984. The cases were indexed from the files of the pathology department and also from demographic and occupational data concerning the patients which had been gathered retrospectively from an inquiry of patients attached either to private physicians or to a hospital service. From 1956 to 1984 there were 125 cases (119 men, 6 women) who had been diagnosed; 92 cases were registered between 1985 and 1992 (79 men and 13 women). An increase in the annual number of cases was significant. The incidence during the period 1985-1992 was 10.9 per million inhabitants (men 19.4, women 3) against 8.7 (men 17.2, women 0.8) for the period 1975 to 1984 and 2.6 (men 5.2, women 0.2) for the period 1956-1974. The mean age of the subjects at the time of diagnosis rose during the period studied (59.2 +/- 9.4 between 1956-1974 to 63.1 +/- 11.9 between 1975-1984 and 67.0 +/- 9.7 between 1985-1992). Occupational exposure to asbestos was certain or probable in 85 per cent of cases with a median duration of exposure of 25 years (range 2 months to 48 years) with a median interval between the first exposure to diagnosis of 44 years (range 10-70 years). The industrial sector most often implicated was naval construction (127 cases).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Amianto/efeitos adversos , Mesotelioma/epidemiologia , Exposição Ocupacional , Neoplasias Pleurais/epidemiologia , Fatores Etários , Idoso , Estudos de Coortes , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais
20.
Rev Pneumol Clin ; 51(2): 87-9, 1995.
Artigo em Francês | MEDLINE | ID: mdl-7569566

RESUMO

The thyroid gland involvement in sarcoidosis is rare but not exceptional. Usually there is little or no clinical expression although hyperthyroidism may be present. The granulomatous infiltration of the thyroid gland cannot be responsible for all the abnormalities observed. In certain cases, there is undoubtedly an autoimmune disease. We report a case of concomitant discovery of sarcoidosis and Hashimoto's thyroiditis. Despite their relative frequency, there could be a relationship between these two pathologies, especially in light of their similar pathophysiology.


Assuntos
Sarcoidose/complicações , Tireoidite Autoimune/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Sarcoidose/fisiopatologia , Tireoidite Autoimune/fisiopatologia
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