RESUMO
INTRODUCTION: Positive professional practice environments are crucial to safeguard a healthy and safe working conditions for health workforce, including nurses; so as to ensure provision of quality healthcare and safety of patient. METHODS: This was a cross-sectional study to assess nurses' perceptions towards nursing practice environment and factors associated with their perceptions. A validated Practice Environment Scale of the Nursing Work Index (PESNWI) questionnaire was administered to nurses working in two Ministry of Health hospitals. The questionnaire comprises of five subscales: Participation, Foundation, Managers Support, Workforce Adequacy and Physician/Nurse Relations. Mean scores of >2.50 were considered as favourable, and ≤2.50 were considered as unfavourable. Simple linear and multiple linear regression analysis were employed to identify factors associated with their perceptions. Analysis was carried out using STATA version 14.0. RESULTS: A total of 366 respondents took part in the study, with a response rate of 98.4%. Majority were working shift (89.6%) and working extended hours (62.3%). In general, the nursing practice environments were rated as favourable. Overall mean score was 2.90±0.03 and four out of five subscales' mean scores were >2.50. Foundation for quality nursing care was perceived as the most favourable subscale, while workforce adequacy was perceived as the least favourable. There were statistically significant association between working extended hours, doing double shift and working during day off with perceived unfavourable workforce adequacy. CONCLUSION: Nursing practice environment was perceived as favourable in the studied hospitals. Policy makers, service providers, and hospital managers could explore further on human resource planning and management of nursing personnel to tackle the issue of nurse staffing in the country.
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Enfermeiras e Enfermeiros , Local de Trabalho , Estudos Transversais , Humanos , Malásia , Percepção , Inquéritos e QuestionáriosRESUMO
Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R). Primary OS analysis was planned after â¼213 OS events and ≥32-month follow-up. OS was analysed by a Cox proportional hazards model, stratified by EGFR mutation type and baseline brain metastases. Results: Two-hundred and twenty-six OS events had occurred at the data cut-off (8 April 2016). After a median follow-up of 42.6 months, median OS (afatinib versus gefitinib) was 27.9 versus 24.5 months [hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.66â1.12, P = 0.2580]. Prespecified subgroup analyses showed similar OS trends (afatinib versus gefitinib) in patients with exon 19 deletion (30.7 versus 26.4 months; HR, 0.83, 95% CI 0.58â1.17, P = 0.2841) and L858R (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62â1.36, P = 0.6585) mutations. Most patients (afatinib, 72.6%; gefitinib, 76.8%) had at least one subsequent systemic anti-cancer treatment following discontinuation of afatinib/gefitinib; 20 (13.7%) and 23 (15.2%) patients received a third-generation EGFR tyrosine kinase inhibitor. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib. Conclusion: In LUX-Lung 7, there was no significant difference in OS with afatinib versus gefitinib. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib. Clinicaltrials.gov identifier: NCT01466660.
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Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Afatinib , Idoso , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptores ErbB/genética , Feminino , Gefitinibe , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Modelos de Riscos Proporcionais , Quinazolinas/farmacologia , Resultado do TratamentoRESUMO
BACKGROUND: This study investigated the activity of MK-2206, an AKT inhibitor, in metastatic or recurrent nasopharyngeal carcinoma (NPC). METHOD: Oral MK-2206 at a dose of 200 mg was administered on days 1, 8, 15 and 22 of a 28-day cycle until progression. Plasma EBV DNA clearance during the first month of treatment was measured, and archived tumors were analyzed for the expression of AKT and PIK3CA mutation and PIK3CA amplification. The dual primary endpoint was objective response rate and 6-month progression-free survival (PFS) rate. RESULTS: 21 patients were enrolled and one patient achieved a partial response (5 %) and 11 had stable disease (52 %), with a median PFS of 3.5 months (95 % confidence interval, CI: 0.9-7.3). The 6-month PFS rate was 43 % (95 % CI: 22-66 %) and the median OS was 10 months (95 % CI: 5.9 months-not reached). Seven patients (33 %) experienced grade 3 toxicities which could be related to MK-2206. Macular-papular rash was the most common (n = 6), followed by hyperglycemia (n = 2) and fatigue (n = 1). In the 12 tumor samples analyzed, PIK3CA amplification was detected in one patient's primary NPC, who had SD lasting over 12 months. Patients with decreasing EBV DNA values over time were more likely to be alive and progression-free for at least 6 months than those without a decrease (p = 0.001). CONCLUSION: The study was terminated due to the limited activity observed in this heavily pre-treated group of patients. Further studies are needed to elucidate the optimal way of selecting patients for AKT inhibitors.
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Antineoplásicos/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Neoplasias Nasofaríngeas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma , DNA Viral/sangue , Intervalo Livre de Doença , Feminino , Herpesvirus Humano 4/genética , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/virologia , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/virologia , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Resultado do TratamentoRESUMO
BACKGROUND: Individuals with metastatic Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) continue to have poor outcomes. To evaluate the ability of a dendritic cell (DC) vaccine to target subdominant EBV antigens LMP1 and LMP2 expressed by NPC cells, we vaccinated patients using autologous DCs transduced with an adenovirus encoding a truncated LMP1 (ΔLMP1) and full-length LMP2 (Ad-ΔLMP1-LMP2). MATERIALS AND METHODS: Sixteen subjects with metastatic NPC received Ad-ΔLMP1-LMP2 DC vaccines i.d. biweekly for up to five doses. Toxicity, immune responses and clinical responses were determined. RESULTS: Most patients had extensive disease, with a median of three visceral sites of involvement (range 1-7). No significant toxicity was observed. Ad-ΔLMP1-LMP2 DCs induced delayed type hypersensitivity responses in 9 out of 12 patients, but although these DCs activated LMP1/2-specific T cells in vitro, no such increase in the frequency of peripheral LMP1/2-specific T cells was detected. Three patients had clinical responses including one with partial response (for 7½ months) and two with stable disease (for 6½ and 7½ months). CONCLUSIONS: Ad-ΔLMP1-LMP2 transduced DCs can be successfully generated and safely administered to patients with advanced NPC. Since efficacy was limited, future studies should focus on DC vaccines with greater potency administered to subjects with less tumor burden.
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Adenoviridae/genética , Vacinas Anticâncer/administração & dosagem , Carcinoma/terapia , Células Dendríticas/imunologia , Neoplasias Nasofaríngeas/terapia , Proteínas da Matriz Viral/imunologia , Adulto , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Carcinoma/mortalidade , Carcinoma/virologia , Células Cultivadas , Técnicas de Cocultura , Células Dendríticas/metabolismo , Células Dendríticas/transplante , Células Dendríticas/virologia , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/complicações , Feminino , Vetores Genéticos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/virologia , Deleção de Sequência , Resultado do Tratamento , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/metabolismoRESUMO
BACKGROUND: Gefitinib was demonstrated to be synergistic with cisplatin and radiotherapy (RT) in in vitro studies. Biomarkers predictive of response to gefitinib in squamous cell head and neck cancer is still lacking. METHODS: Thirty-one patients with locally advanced and easily accessible primary tumor sites for biopsies were recruited. Gefitinib was started 3 weeks before the start of cisplatin/concurrent radiotherapy (CTRT) and continued during the CTRT phase and thereafter for 4 months as consolidation phase. Two baselines and a repeat tumor sample were taken after 2 weeks of gefitinib alone to study its impact on tumor gene expression. Epidermal growth factor receptor (EGFR) protein expression, FISH and mutational status, and matrix metallopeptidase 11 (MMP11) protein expression were correlated with response and survival outcome. RESULTS: The overall response rate to gefitinib alone was 9.7%. The survival outcome is as follows: median disease free 1.3 years, median survival time 2.4 years, 3-year disease free 42.9%, and 3-year overall survival 48.4%. EGFR FISH, protein expression, and mutational status did not predict for response nor survival outcome of patients. Although MMP11 overexpression did not predict for response, it predicted significantly for a poorer survival outcome. CONCLUSIONS: Gefitinib can be combined safely with cisplatin/RT. More studies are needed to uncover predictive biomarkers of benefit to gefitinib.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Quimiorradioterapia , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/terapia , Adulto , Idoso , Biomarcadores Tumorais/genética , Cisplatino/administração & dosagem , Análise Mutacional de DNA , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Gefitinibe , Expressão Gênica , Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Hibridização in Situ Fluorescente , Masculino , Metaloproteinase 11 da Matriz/genética , Metaloproteinase 11 da Matriz/metabolismo , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Quinazolinas/administração & dosagem , Fatores de Risco , Fumar , Resultado do TratamentoRESUMO
BACKGROUND: This open-label phase III study assessed the addition of Toll-like receptor 9-activating oligodeoxynucleotide PF-3512676 to gemcitabine/cisplatin chemotherapy in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomized (1:1) to receive six or fewer 3-week cycles of i.v. gemcitabine (1250 mg/m2 on days 1 and 8) and cisplatin alone (75 mg/m2 on day 1, control arm) or combined with s.c. PF-3512676 0.2 mg/kg on days 8 and 15 of each chemotherapy cycle and weekly thereafter until progression or unacceptable toxicity (experimental arm). No crossover was planned. The primary end point was overall survival (OS). RESULTS: A total of 839 patients were randomized. Baseline demographics were well balanced. Median OS (11.0 versus 10.7 months; P=0.98) and median progression-free survival (PFS) (both 5.1 months) were similar between groups. Grade≥3 hematologic adverse events (AEs), injection-site reactions, and influenza-like symptoms were more frequently reported among patients receiving PF-3512676. At the first-interim analysis, the Data Safety Monitoring Committee recommended study discontinuation. Administration of PF-3512676 was halted based on efficacy futility and increased grade≥3 AEs (experimental arm). CONCLUSIONS: Addition of PF-3512676 to gemcitabine/cisplatin chemotherapy did not improve OS or PFS but did increase toxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Oligodesoxirribonucleotídeos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oligodesoxirribonucleotídeos/efeitos adversos , Modelos de Riscos Proporcionais , GencitabinaRESUMO
BACKGROUND: To evaluate the efficacy and toxicity of single-agent docetaxel (Taxotere) as therapy in patients with disseminated nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Patients with histologically confirmed metastatic or recurrent NPC who have failed at least one line of palliative chemotherapy regimen but no prior docetaxel were eligible. Patients received weekly docetaxel every 28 days (docetaxel 30 mg/m(2) on days 1, 8 and 15) and were evaluated every two cycles of treatment of response assessment. Quality-of-life (QoL) assessments during the treatment period were done using the European Organization for Research and Treatment of Cancer QoL questionnaire QLQ-C30; version 3.0. RESULTS: Thirty patients were assessable for toxicity and response. The median age of the patients was 47 years (range 25-68 years) and the majority of patients had good performance status (Eastern Cooperative Oncology Group 0-1). Grade 3 or 4 toxicity included fatigue (13%), anemia (10%) and diarrhea (3%) of patients. Eleven (37%) and four (13.3%) patients achieved partial response and stable disease, respectively. The median progression-free survival was 5.3 months and median overall survival of 12.8 months. The partial responders had a mean duration of response of 4.1 months. Docetaxel caused a significant decline in QoL scores during treatment of patients responding or progressing with the treatment. CONCLUSIONS: Our findings suggest that weekly docetaxel is well tolerated and is an active agent in patients with disseminated NPC who were previously exposed and largely refractory to platinum-based chemotherapy but can cause a significant decline in QoL during treatment.
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Antineoplásicos/uso terapêutico , Neoplasias Nasofaríngeas/tratamento farmacológico , Taxoides/uso terapêutico , Adulto , Idoso , Carcinoma , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Metástase Neoplásica , Cuidados Paliativos , Qualidade de Vida , Falha de TratamentoRESUMO
BACKGROUND: The aim of this study was to determine the maximum tolerated dose (MTD) and the pharmacokinetic profile of Genexol-PM in Asian cancer patients. MATERIALS AND METHODS: Patients (N = 24) refractory to previous chemotherapy received Genexol-PM as an 1-h infusion on a weekly basis for 3 weeks followed by a resting week. The starting dose was 80 mg/m(2) and the maximum administered dose was 200 mg/m(2). RESULTS: The majority of patients had lung, nasopharyngeal and breast cancers and in eleven patients (46%), taxane-based chemotherapy had previously failed. The MTD was defined at 180 mg/m(2). The most common grade 3 non-hematologic adverse events in cycle 1 were fatigue (4%) and neuropathy (4%) occurring mainly at 200 mg/m(2). Five (21%) patients had partial response, nine (38%) had stable disease and seven (29%) had disease progression. Five of 11 previously taxane-refractory patients showed clinical benefit to Genexol-PM. The pharmacokinetics of Genexol-PM displayed dose-proportionality, with both the maximum concentration (C(max)) and the area under the concentration-time curve from zero to infinity (AUC(0-infinity)) increasing by approximately four- and threefold, respectively, as the dose of Genexol-PM was escalated from 80 to 200 mg/m(2). The median total-body clearance of Genexol-PM for all patients was 43.9 l/h. CONCLUSION: The weekly regimen of Genexol-PM was well tolerated and responses were observed in patients with refractory tumors, including patients who had failed taxane-based chemotherapy previously.
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Neoplasias/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/farmacocinética , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Química Farmacêutica , Esquema de Medicação , Feminino , Humanos , Lipossomos/efeitos adversos , Lipossomos/farmacocinética , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/metabolismo , Neoplasias/patologia , Paclitaxel/efeitos adversos , Terapia de Salvação , Resultado do TratamentoRESUMO
BACKGROUND: Identification of appropriate markers for predicting clinical benefit with erlotinib in non-small-cell lung cancer (NSCLC) may be able to guide patient selection for treatment. This open-label, multicentre, phase II trial aimed to identify genes with potential use as biomarkers for clinical benefit from erlotinib therapy. METHODS: Adults with stage IIIb/IV NSCLC in whom one or more chemotherapy regimen had failed were treated with erlotinib (150 mg/day). Tumour biopsies were analysed using gene expression profiling with Affymetrix GeneChip microarrays. Differentially expressed genes were verified using quantitative RT-PCR (qRT-PCR). RESULTS: A total of 264 patients were enrolled in the study. Gene expression profiles found no statistically significant differentially expressed genes between patients with and without clinical benefit. In an exploratory analysis in responding versus nonresponding patients, three genes on chromosome 7 were expressed at higher levels in the responding group [epidermal growth factor receptor (EGFR), phosphoserine phosphatase (PSPH) and Rap guanine nucleotide exchange factor 5 (RAPGEF5)]. Independent quantification using qRT-PCR validated the association between EGFR and PSPH overexpression, but not RAPGEF5 overexpression, and clinical outcome. CONCLUSIONS: This study supports the use of erlotinib as an alternative to chemotherapy for patients with relapsed advanced NSCLC. Genetic amplification of the EGFR region of chromosome 7 may be associated with response to erlotinib therapy.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Perfilação da Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Biomarcadores Farmacológicos/análise , Biomarcadores Farmacológicos/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Intervalo Livre de Doença , Cloridrato de Erlotinib , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Quinazolinas/efeitos adversosRESUMO
BACKGROUND: The study compared the efficacy of a first-line treatment with day 1 i.v. vinorelbine (NVBiv) and day 8 oral vinorelbine (NVBo) versus docetaxel (DCT) in a cisplatin-based combination in advanced non-small-cell lung cancer, in terms of time to treatment failure (TTF), overall response, progression-free survival (PFS), overall survival (OS), tolerance and quality of life (QoL). METHODS: Patients were randomly assigned to receive cisplatin 80 mg/m2 with NVBiv 30 mg/m2 on day 1 and NVBo 80 mg/m2 on day 8 every 3 weeks, after a first cycle of NVBiv 25 mg/m2 on day 1 and NVBo 60 mg/m2 on day 8 (arm A) or cisplatin 75 mg/m2 and DCT 75 mg/m2 on day 1 every 3 weeks (arm B), for a maximum of six cycles in both arms. RESULTS: From 2 February 2004 to 1 January 2006, 390 patients were entered in a randomised study and 381 were treated. The patient characteristics are as follows (arms A/B): metastatic (%) 80.5/84.8; patients with three or more organs involved (%) 45.3/40.8; median age 59.4/62.1 years; male 139/146; squamous (%) 34.2/33.5; adenocarcinoma (%) 41.6/39.3; median TTF (arms A/B in months) [95% confidence interval (CI)]: 3.2 (3.0-4.2), 4.1 (3.4-4.5) (P = 0.19); overall response (arms A/B) (95% CI): 27.4% (21.2% to 34.2%), 27.2% (21.0% to 34.2%); median PFS (arms A/B in months) (95% CI): 4.9 (4.4-5.9), 5.1 (4.3-6.1) (P = 0.99) and median OS (arms A/B in months) (95% CI): 9.9 (8.4-11.6), 9.8 (8.8-11.5) (P = 0.58). The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B, respectively. Main haematological toxicity was grade 3-4 neutropenia: 24.4% (arm A) and 28.8% (arm B). QoL as measured by the Lung Cancer Symptom Scale was similar in both arms. CONCLUSIONS: Both arms provided similar efficacy in terms of response, time-related parameters and QoL, with an acceptable tolerance profile. In the current Global Lung Oncology Branch trial 3, NVBo was shown to be effective as a substitute for the i.v. formulation. This can relieve the burden of the i.v. injection on day 8 and can optimise the hospital's resources and improve patient convenience.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Administração Oral , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Terapia Combinada , Intervalo Livre de Doença , Docetaxel , Esquema de Medicação , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Masculino , Estudos Prospectivos , Qualidade de Vida , Análise de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
BACKGROUND: Accurate total body surface area burned (TBSAB) estimation is a crucial aspect of early burn management. It helps guide resuscitation and is essential in the calculation of fluid requirements. Conventional methods of estimation can often lead to large discrepancies in burn percentage estimation. We aim to compare a new method of TBSAB estimation using a three-dimensional smart-phone application named 3D Burn Resuscitation (3D Burn) against conventional methods of estimation-Rule of Palm, Rule of Nines and the Lund and Browder chart. METHODS: Three volunteer subjects were moulaged with simulated burn injuries of 25%, 30% and 35% total body surface area (TBSA), respectively. Various healthcare workers were invited to use both the 3D Burn application as well as the conventional methods stated above to estimate the volunteer subjects' burn percentages. RESULTS: Collective relative estimations across the groups showed that when used, the Rule of Palm, Rule of Nines and the Lund and Browder chart all over-estimated burns area by an average of 10.6%, 19.7%, and 8.3% TBSA, respectively, while the 3D Burn application under-estimated burns by an average of 1.9%. There was a statistically significant difference between the 3D Burn application estimations versus all three other modalities (p < 0.05). Time of using the application was found to be significantly longer than traditional methods of estimation. CONCLUSIONS: The 3D Burn application, although slower, allowed more accurate TBSAB measurements when compared to conventional methods. The validation study has shown that the 3D Burn application is useful in improving the accuracy of TBSAB measurement. Further studies are warranted, and there are plans to repeat the above study in a different centre overseas as part of a multi-centre study, with a view of progressing to a prospective study that compares the accuracy of the 3D Burn application against conventional methods on actual burn patients.
RESUMO
INTRODUCTION: The aim of this study was to assess toxicity and response in the sequential administration of gemcitabine followed by cisplatin in unresectable or metastatic non-small cell lung cancer. MATERIALS AND METHODS: Twenty-three patients were enrolled in this study. Gemcitabine was given at 1,250 mg/m2 on days 1 and 8, for four 21-day cycles. RESULTS: There were 4 patients with partial responses. 5 patients with stable disease and 10 patients with progressive disease, giving a response rate of 21%. The median time to disease progression was 3.3 months. The median overall survival was 14.6 months. Toxicities graded 3 or 4 included anaemia (13.0%), neutropaenia (13.0%), supraventricular tachycardia (4.3%), and nausea and vomiting (4.3%). CONCLUSION: Although these results show similar efficacy to single-agent treatment regimens, the low toxicity profile and promising survival outcome with this regimen are important points for consideration.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Singapura , GencitabinaRESUMO
PURPOSE: The objective of this trial was to compare two vinorelbine-based doublets with carboplatin (CBDCA-VC) or with gemcitabine (VG) in patients with stage IIIB-IV non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 316 patients with advanced NSCLC previously untreated were randomized to either vinorelbine 30 mg/m(2) D1,8 with carboplatin AUC 5 D1 (VC) or vinorelbine 25mg/m(2) with gemcitabine (VG) 1000 mg/m(2) both given D1,8 every 3 weeks. The primary endpoint was response rate with secondary parameters being survival (OS), progression-free survival (PFS), tolerance and clinical benefit. RESULTS: The median number of cycles was four in each arm with a total of 1268 cycles. The objective response (OR) on intent-to-treat was 20.8% in VC and 28% in VG (p=0.15). Median PFS was 3.9 months in VC and 4.4 months (mo) in VG (p=0.18). Median survival was significantly longer (p=0.01) for VG with 11.5 mo compared to 8.6 mo in VC with 1 year survival at 48.9 and 34.4%, respectively. Tolerance was better in the VG arm as compared to the VC patients. Four toxic deaths were recorded in the VC group. Clinical benefit response rate was 32.4% compared to 40.9% in 111 and 110 evaluable patients in VC and VG, respectively. CONCLUSION: VG compared to VC resulted in a similar overall response rate, favourable median survival and a better toxicity profile. For non-cisplatin-based chemotherapy, VG is a useful alternative.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adolescente , Adulto , Idoso , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/secundário , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Agências Internacionais , Neoplasias Pulmonares/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , GencitabinaRESUMO
INTRODUCTION: Data on combined modality treatment for locally advanced squamous cell carcinoma of the oesophagus involving Asian patients are limited. MATERIALS AND METHODS: A retrospective study of 56 consecutive patients with this condition treated with concurrent chemoradiotherapy followed by surgery in a single tertiary institution in Singapore was performed. RESULTS: The median overall survival of the entire cohort was 14.1 months [95% confidence interval (CI); range, 8.6 to 19.6 months]. In patients who underwent successful oesophagectomy after chemoradiotherapy (n = 17), the median survival was 27.8 months compared to 9.8 months for those who did not have surgery (n = 39) (P = 0.046, log-rank test). The median time to first relapse for the entire cohort was 16.1 months (95% CI, 7.7 to 24.5 months). The time to first relapse was 23.9 months in the subgroup of patients with successful surgery and 12.1 months in the group which did not (P = 0.147, log-rank test). The high proportion of patients who were medically unfit for surgery or declined surgery may have conferred a selection bias. CONCLUSION: Concurrent chemoradiotherapy followed by surgery is feasible in selected patients. The benefit of adding of surgery to chemoradiotherapy is still controversial and we await the results of randomised controlled trials comparing chemoradiotherapy with surgery versus chemoradiotherapy alone.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/radioterapia , Esofagectomia , Humanos , Estudos RetrospectivosRESUMO
AIMS: Adenoid cystic carcinoma of the lower respiratory tract is a rare indolent neoplasm with prolonged survival, propensity for recurrences and metastasis years after initial therapy. We aim to study a 1,700-bed single tertiary academic hospital's long-term experience with ACC of the lower respiratory tract from the larynx to the lungs and review published literature on this subject. MATERIALS AND METHODS: We analysed the clinicopathology, treatment options and outcome in 33 patients and reviewed the published literature over the last five decades. RESULTS: The tumour has no gender predilection, a peak incidence in the fifth decade and is not related to smoking. Insidious symptoms are often treated as benign obstructive airway disease and infection; negative signs and normal chest X-rays delayed diagnosis. The tumour was distributed most commonly in the trachea followed by main bronchi, lobar bronchi and larynx. About 22% of patients required emergent bronchoscopic intervention to secure airway patency before definitive therapy with surgery or/and radiotherapy. A high proportion of resected specimens had positive margins. Overall survival and disease-free survival rates at 5 years were 81 and 62%, respectively, and at 10 years 70 and 54%, respectively. Prolonged good palliation was achieved for patients with unresectable lesions with radiation and wide armamentarium of endoscopic therapy. CONCLUSIONS: In time, many patients eventually succumb to this disease. However, advances in medical skill and technology have prolonged survival while maintaining a good quality of life. Adenoid cystic carcinoma of the respiratory tract is a chronic life-long disease that may require interval intensive therapy. The challenge is to find the best therapeutic regimen aiming for a 'true' cure. Further study on the mutational landscape of adenoid cystic carcinoma may provide potential avenues for novel treatments to address a chemoresistant cancer.
Assuntos
Carcinoma Adenoide Cístico/terapia , Recidiva Local de Neoplasia/terapia , Qualidade de Vida , Neoplasias do Sistema Respiratório/terapia , Adulto , Idoso , Carcinoma Adenoide Cístico/patologia , Terapia Combinada , Gerenciamento Clínico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Cuidados Paliativos , Prognóstico , Neoplasias do Sistema Respiratório/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemAssuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Neoplasias Nasofaríngeas/tratamento farmacológico , Viagem , Capecitabina , Desoxicitidina/efeitos adversos , Dermatoglifia , Emigração e Imigração , Dedos , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Pele/efeitos dos fármacos , Estados UnidosRESUMO
The survival outcome of patients with systemic cancer differs significantly between individuals even within the same tumour type. We set out to illustrate this by analysing the factors determining survival in patients with metastatic disease from nasopharyngeal carcinoma (NPC) and to design a scoring system based on these prognostic factors. Patients referred between January 1994 and December 1999 were retrospectively analysed. Factors analysed included patient (age group, gender, performance status (BS) at diagnosis of metastases), disease (number of metastatic sites, specific metastatic sites, disease-free interval (DFI), metastases at presentation, presence of locoregional recurrence), and laboratory factors (leucocyte count, haemoglobin level, albumin level). Univariate and multivariable analyses were performed using the Cox proportion hazards model. A numerical score was derived from the regression coefficients of each independent prognostic variable. The prognostic index score (PIS) of each patient was calculated by totalling up the scores of each independent variable. Independently significant, negative prognostic factors were liver metastasis, lung metastasis, anaemia, poor PS, distant metastasis at initial diagnosis, and a DFI of <6 months. Three prognostic groups based on the PIS were obtained: (i) good risk (PIS=0-6); (ii) intermediate risk (7-10); (iii) poor risk (>or=11). The median survivals for these groups were 19.5, 10, and 5.8, months, respectively, (log rank test: P<0.0001). The variable prognosis of patients with disseminated NPC can be assessed by using easily available clinical information (patient, disease and laboratory factors). The PIS system will need to be validated on prospectively collected data of another cohort of patients.
Assuntos
Neoplasias Nasofaríngeas/mortalidade , Adulto , Idoso , Antineoplásicos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Nasofaríngeas/tratamento farmacológico , Metástase Neoplásica , Recidiva Local de Neoplasia , Cuidados Paliativos , Prognóstico , Análise de Regressão , Análise de SobrevidaRESUMO
PURPOSE: Nasopharyngeal carcinoma (NPC) is endemic in Singapore. Nearly 60% of the patients diagnosed with NPC will present with locally advanced disease. The North American Intergroup study 0099 reported improved survival outcome in patients with locally advanced NPC who received combined chemoradiotherapy when compared to radiotherapy alone. Hence we explored the feasibility and efficacy of a similar protocol in our patients. METHODS AND MATERIALS: Between June 1996 and December 1997, 57 patients were treated with the following schedule as described. Radical radiotherapy (RT) of 66-70 Gy to the primary and neck with cisplatin (CDDP) 25 mg/m2 on days 1-4 given by infusion over 6-8 hours daily on weeks 1, 4, and 7 of the RT. This is followed by a further 3 cycles of adjuvant chemotherapy starting from week 11 from the first dose of radiation (CDDP 20 mg/m2/d and 5-fluorouracil [5-FU] 1 gm/m2/d on days 1-4 every 28 days). RESULTS: The majority of patients (68%) had Stage IV disease. About 54% of patients received all the intended treatment; 75% received all 3 cycles of CDDP during the RT phase and 63% received all three cycles of adjuvant chemotherapy. The received dose intensity of CDDP and 5-FU of greater than 0.8 was achieved in 58% and 60% of the patients respectively. Two treatment-related deaths due to reactivation of hepatitis B and neutropenic sepsis respectively, were encountered. At median follow-up of 16 months, 14 patients had relapsed, 12 systemically and 2 loco-regionally. CONCLUSION: Due to the acceptable tolerability of such a protocol in our cohort of patients, we have embarked on a Phase III study to confirm the results of the 0099 Intergroup study in the Asian context.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Rim/efeitos dos fármacos , Rim/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Dosagem RadioterapêuticaRESUMO
BACKGROUND: Patients who present with malignant pleural/malignant effusion without a definite primary site are not well described in the medical literature. In the course of our clinical practice, we have observed certain traits that are peculiar to patients with such a presentation. We have applied the term primary intrathoracic malignant effusion (PIME) to describe this condition. STUDY OBJECTIVES: Patients must fulfill the following criteria before a diagnosis of PIME can be made: clinical presentation dominated by pleural/pericardial effusion; histologic proof of malignancy obtained from the pleura and/or pericardium; no definite primary site in the lungs or elsewhere from CT scan of the chest, chest radiograph, or physical and endoscopic examination; no history of malignancy; and no history of asbestos exposure. Exposure to environmental tobacco smoke (ETS) among the nonsmokers was examined in a case-control setting. METHODS: We conducted a retrospective search of our database of patients who were referred to the Department of Medical Oncology with a diagnosis of pleural/pericardial effusion from January 1993 to January 2000. RESULTS: Seventy-one of 200 patients from our database met the criteria. A significant majority of the patients were women (65%) and nonsmokers (72%). All patients had adenocarcinoma shown on biopsy. The majority of patients (63%) had disease localized to the intrathoracic serosal surfaces; the rest had distant metastases involving the lung (50%), bone (27%), liver (19%), brain (8%), and skin (4%). Six patients had two or more sites of distant metastases. There was a significant association with ETS exposure when compared to a control group comprised of patients with colonic cancer, matched for sex and age. The median survival was 10 months for patients with disease localized to the pleura/pericardium and 7 months for those with distant metastases. Thirty-eight patients (54%) received chemotherapy. All had platinum-based chemotherapy, except for three patients. The median survival for patients treated or not treated with chemotherapy was 12 months and 5 months, respectively. This difference in survival was statistically significant (p = 0.003). CONCLUSIONS: PIME should be viewed as a distinct entity. Its etiology remains largely unknown, although exposure to environmental tobacco smoke may play a part. Platinum-based chemotherapy may have a positive biological effect on this disease. More studies are required to elucidate the epidemiology, possible etiologic factors, and treatment options for this group of patients.
Assuntos
Neoplasias Primárias Desconhecidas , Derrame Pericárdico/etiologia , Derrame Pleural Maligno , Derrame Pleural Maligno/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/mortalidade , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/mortalidade , Estudos Retrospectivos , Fumar , Taxa de SobrevidaRESUMO
Studies using mainly dietary restriction have shown that weight loss is associated with a decrease in fat-free mass (FFM) and resting energy expenditure (REE). The aim of this study was to investigate the effects of a weight-loss program relying solely on increased physical activity on FFM and REE. Forty-two overweight male military recruits (12 with initial body mass index [BMI] between 25.0 and 29.9 kg/m2, group 1; 14 with BMI between 30.0 and 34.9 kg/m2, group 2; and 16 with BMI of at least 35 kg/m2, group 3) completed a 5-month program of supervised physical activity that included both aerobic and muscle-strengthening components. All subjects lost significant amounts of weight (group 1, 8.6 kg; group 2, 15.7 kg; group 3, 22.0 kg). This weight loss was accompanied by a significant reduction in the waist to hip ratio (WHR) in all groups. FFM was maintained in all groups. REE tended to decline in all groups (group 1, from 1,595.0 +/- 46.9 to 1,511.7 +/- 53.2 kcal/d; group 2, from 1,751.4 +/- 56.0 to 1,680.0 +/- 63.1 kcal/d; group 3, from 1,901.9 +/- 93.7 to 1,740.0 +/- 67.3 kcal/d), but this decline reached statistical significance only when all 42 subjects were considered. REE normalized for FFM did not decrease except in group 1. Furthermore, differences between the slopes and intercepts of the regression lines relating REE with FFM before and at completion of the 5-month program were not statistically significant, suggesting that the relationship between REE and FFM was maintained after weight loss.(ABSTRACT TRUNCATED AT 250 WORDS)