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1.
N Engl J Med ; 389(21): 1935-1948, 2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-37937763

RESUMEN

BACKGROUND: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that is selective for EGFR-TKI-sensitizing and EGFR T790M resistance mutations. Evidence suggests that the addition of chemotherapy may extend the benefits of EGFR-TKI therapy. METHODS: In this phase 3, international, open-label trial, we randomly assigned in a 1:1 ratio patients with EGFR-mutated (exon 19 deletion or L858R mutation) advanced non-small-cell lung cancer (NSCLC) who had not previously received treatment for advanced disease to receive osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg per square meter of body-surface area] plus either cisplatin [75 mg per square meter] or carboplatin [pharmacologically guided dose]) or to receive osimertinib monotherapy (80 mg once daily). The primary end point was investigator-assessed progression-free survival. Response and safety were also assessed. RESULTS: A total of 557 patients underwent randomization. Investigator-assessed progression-free survival was significantly longer in the osimertinib-chemotherapy group than in the osimertinib group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.49 to 0.79; P<0.001). At 24 months, 57% (95% CI, 50 to 63) of the patients in the osimertinib-chemotherapy group and 41% (95% CI, 35 to 47) of those in the osimertinib group were alive and progression-free. Progression-free survival as assessed according to blinded independent central review was consistent with the primary analysis (hazard ratio, 0.62; 95% CI, 0.48 to 0.80). An objective (complete or partial) response was observed in 83% of the patients in the osimertinib-chemotherapy group and in 76% of those in the osimertinib group; the median response duration was 24.0 months (95% CI, 20.9 to 27.8) and 15.3 months (95% CI, 12.7 to 19.4), respectively. The incidence of grade 3 or higher adverse events from any cause was higher with the combination than with monotherapy - a finding driven by known chemotherapy-related adverse events. The safety profile of osimertinib plus pemetrexed and a platinum-based agent was consistent with the established profiles of the individual agents. CONCLUSIONS: First-line treatment with osimertinib-chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR-mutated advanced NSCLC. (Funded by AstraZeneca; FLAURA2 ClinicalTrials.gov number, NCT04035486.).


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Inhibidores de Proteínas Quinasas , Humanos , Compuestos de Anilina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Pemetrexed/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Antineoplásicos/uso terapéutico
2.
Lancet ; 389(10072): 917-929, 2017 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-28126333

RESUMEN

BACKGROUND: The efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is not known. We assessed the efficacy and safety of ceritinib versus platinum-based chemotherapy in these patients. METHODS: This randomised, open-label, phase 3 study in untreated patients with stage IIIB/IV ALK-rearranged non-squamous NSCLC was done in 134 centres across 28 countries. Eligible patients were assigned via interactive response technology to oral ceritinib 750 mg/day or platinum-based chemotherapy ([cisplatin 75 mg/m2 or carboplatin AUC 5-6 plus pemetrexed 500 mg/m2] every 3 weeks for four cycles followed by maintenance pemetrexed); randomisation was stratified by World Health Organization performance status (0 vs 1-2), previous neoadjuvant or adjuvant chemotherapy, and presence of brain metastases as per investigator's assessment at screening. Investigators and patients were not masked to treatment assignment. The primary endpoint was blinded independent review committee assessed progression-free survival, based on all randomly assigned patients (the full analysis set). Efficacy analyses were done based on the full analysis set. All safety analyses were done based on the safety set, which included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01828099. FINDINGS: Between Aug 19, 2013, and May 11, 2015, 376 patients were randomly assigned to ceritinib (n=189) or chemotherapy (n=187). Median progression-free survival (as assessed by blinded independent review committee) was 16·6 months (95% CI 12·6-27·2) in the ceritinib group and 8·1 months (5·8-11·1) in the chemotherapy group (hazard ratio 0·55 [95% CI 0·42-0·73]; p<0·00001). The most common adverse events were diarrhoea (in 160 [85%] of 189 patients), nausea (130 [69%]), vomiting (125 [66%]), and an increase in alanine aminotransferase (114 [60%]) in the ceritinib group and nausea (in 97 [55%] of 175 patients), vomiting (63 [36%]), and anaemia (62 [35%]) in the chemotherapy group. INTERPRETATION: First-line ceritinib showed a statistically significant and clinically meaningful improvement in progression-free survival versus chemotherapy in patients with advanced ALK-rearranged NSCLC. FUNDING: Novartis Pharmaceuticals Corporation.


Asunto(s)
Antineoplásicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Pirimidinas/administración & dosificación , Sulfonas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pemetrexed/administración & dosificación , Pemetrexed/efectos adversos , Pirimidinas/efectos adversos , Sulfonas/efectos adversos , Resultado del Tratamiento , Adulto Joven
3.
Lancet Oncol ; 16(2): 141-51, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25589191

RESUMEN

BACKGROUND: We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label, randomised, phase 3 trials. METHODS: Previously untreated patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma were enrolled in LUX-Lung 3 (n=345) and LUX-Lung 6 (n=364). These patients were randomly assigned in a 2:1 ratio to receive afatinib or chemotherapy (pemetrexed-cisplatin [LUX-Lung 3] or gemcitabine-cisplatin [LUX-Lung 6]), stratified by EGFR mutation (exon 19 deletion [del19], Leu858Arg, or other) and ethnic origin (LUX-Lung 3 only). We planned analyses of mature overall survival data in the intention-to-treat population after 209 (LUX-Lung 3) and 237 (LUX-Lung 6) deaths. These ongoing studies are registered with ClinicalTrials.gov, numbers NCT00949650 and NCT01121393. FINDINGS: Median follow-up in LUX-Lung 3 was 41 months (IQR 35-44); 213 (62%) of 345 patients had died. Median follow-up in LUX-Lung 6 was 33 months (IQR 31-37); 246 (68%) of 364 patients had died. In LUX-Lung 3, median overall survival was 28.2 months (95% CI 24.6-33.6) in the afatinib group and 28.2 months (20.7-33.2) in the pemetrexed-cisplatin group (HR 0.88, 95% CI 0.66-1.17, p=0.39). In LUX-Lung 6, median overall survival was 23.1 months (95% CI 20.4-27.3) in the afatinib group and 23.5 months (18.0-25.6) in the gemcitabine-cisplatin group (HR 0.93, 95% CI 0.72-1.22, p=0.61). However, in preplanned analyses, overall survival was significantly longer for patients with del19-positive tumours in the afatinib group than in the chemotherapy group in both trials: in LUX-Lung 3, median overall survival was 33.3 months (95% CI 26.8-41.5) in the afatinib group versus 21.1 months (16.3-30.7) in the chemotherapy group (HR 0.54, 95% CI 0.36-0.79, p=0.0015); in LUX-Lung 6, it was 31.4 months (95% CI 24.2-35.3) versus 18.4 months (14.6-25.6), respectively (HR 0.64, 95% CI 0.44-0.94, p=0.023). By contrast, there were no significant differences by treatment group for patients with EGFR Leu858Arg-positive tumours in either trial: in LUX-Lung 3, median overall survival was 27.6 months (19.8-41.7) in the afatinib group versus 40.3 months (24.3-not estimable) in the chemotherapy group (HR 1.30, 95% CI 0.80-2.11, p=0.29); in LUX-Lung 6, it was 19.6 months (95% CI 17.0-22.1) versus 24.3 months (19.0-27.0), respectively (HR 1.22, 95% CI 0.81-1.83, p=0.34). In both trials, the most common afatinib-related grade 3-4 adverse events were rash or acne (37 [16%] of 229 patients in LUX-Lung 3 and 35 [15%] of 239 patients in LUX-Lung 6), diarrhoea (33 [14%] and 13 [5%]), paronychia (26 [11%] in LUX-Lung 3 only), and stomatitis or mucositis (13 [5%] in LUX-Lung 6 only). In LUX-Lung 3, neutropenia (20 [18%] of 111 patients), fatigue (14 [13%]) and leucopenia (nine [8%]) were the most common chemotherapy-related grade 3-4 adverse events, while in LUX-Lung 6, the most common chemotherapy-related grade 3-4 adverse events were neutropenia (30 [27%] of 113 patients), vomiting (22 [19%]), and leucopenia (17 [15%]). INTERPRETATION: Although afatinib did not improve overall survival in the whole population of either trial, overall survival was improved with the drug for patients with del19 EGFR mutations. The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials. FUNDING: Boehringer Ingelheim.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Mutación/genética , Quinazolinas/uso terapéutico , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Afatinib , Anciano , Anciano de 80 o más Años , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Receptores ErbB/antagonistas & inhibidores , Femenino , Estudios de Seguimiento , Glutamatos/administración & dosificación , Guanina/administración & dosificación , Guanina/análogos & derivados , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pemetrexed , Pronóstico , Tasa de Supervivencia , Gemcitabina
4.
J Med Assoc Thai ; 98(5): 501-7, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-26058280

RESUMEN

OBJECTIVE: Explore the definitive diagnoses of imaging-guided transthoracic needle biopsies (TNB) with a pathological result of benign non-specific diagnosis in a tuberculosis-endemic area. The secondary goal was to characterize the initial CT imaging findings between malignancy and benign lesions. MATERIAL AND METHOD: All TNB diagnoses considered to have benign non-specific features at the Radiology Department between January 2007 andDecember 2011 were retrospectively reviewedfor definitive diagnosis based on clinical impressions andfor CT imaging characteristics. RESULTS: Sixty-seven cases with TNB were given a benign non-specific diagnosis and had complete pathologic or radiologic follow-ups. Of these 67 cases, 16 (23.9%) were malignant and 51 were benign. Two main definitive diagnoses of benign cases were pulmonary tuberculosis (32.8%) and pneumonia/lung abscess (23.9%). On the CT images, most of lesions in the group of pulmonary tuberculosis (14/22, 63.6%) were not enhanced after contrast administration (p < 0.005), and necrotic mediastinal lymph nodes were significantly found more in final malignancy diagnoses (p < 0.005). CONCLUSION: The definitive diagnoses of benign non-specific diagnoses based on TNB in this tuberculosis-endemic area had a high rate of both malignancy and pulmonary tuberculosis. Hence, repeated biopsies or radiological follow-ups are advised.


Asunto(s)
Biopsia Guiada por Imagen/métodos , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/patología , Tomografía Computarizada por Rayos X , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/patología
5.
Lancet Oncol ; 15(2): 213-22, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24439929

RESUMEN

BACKGROUND: Afatinib-an oral irreversible ErbB family blocker-improves progression-free survival compared with pemetrexed and cisplatin for first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). We compared afatinib with gemcitabine and cisplatin-a chemotherapy regimen widely used in Asia-for first-line treatment of Asian patients with EGFR mutation-positive advanced NSCLC. METHODS: This open-label, randomised phase 3 trial was done at 36 centres in China, Thailand, and South Korea. After central testing for EGFR mutations, treatment-naive patients (stage IIIB or IV cancer [American Joint Committee on Cancer version 6], performance status 0-1) were randomly assigned (2:1) to receive either oral afatinib (40 mg per day) or intravenous gemcitabine 1000 mg/m(2) on day 1 and day 8 plus cisplatin 75 mg/m(2) on day 1 of a 3-week schedule for up to six cycles. Randomisation was done centrally with a random number-generating system and an interactive internet and voice-response system. Randomisation was stratified by EGFR mutation (Leu858Arg, exon 19 deletions, or other; block size three). Clinicians and patients were not masked to treatment assignment, but the independent central imaging review group were. Treatment continued until disease progression, intolerable toxic effects, or withdrawal of consent. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). This study is registered with ClinicalTrials.gov, NCT01121393. FINDINGS: 910 patients were screened and 364 were randomly assigned (242 to afatinib, 122 to gemcitabine and cisplatin). Median progression-free survival was significantly longer in the afatinib group (11·0 months, 95% CI 9·7-13·7) than in the gemcitabine and cisplatin group (5·6 months, 5·1-6·7; hazard ratio 0·28, 95% CI 0·20-0·39; p<0·0001). The most common treatment-related grade 3 or 4 adverse events in the afatinib group were rash or acne (35 [14·6%] of 239 patients), diarrhoea (13 [5·4%]), and stomatitis or mucositis (13 [5·4%]), compared with neutropenia (30 [26·5%] of 113 patients), vomiting (22 [19·5%]), and leucopenia (17 [15·0%]) in the gemcitabine and cisplatin group. Treatment-related serious adverse events occurred in 15 (6·3%) patients in the afatinib group and nine (8·0%) patients in the gemcitabine and cisplatin group. INTERPRETATION: First-line afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation-positive advanced lung NSCLC. Afatinib should be considered as a first-line treatment option for this patient population. FUNDING: Boehringer Ingelheim.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pueblo Asiatico/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinazolinas/uso terapéutico , Afatinib , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/etnología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , China/epidemiología , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Receptores ErbB/antagonistas & inhibidores , Femenino , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Modelos Lineales , Modelos Logísticos , Neoplasias Pulmonares/etnología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Inhibidores de Proteínas Quinasas/efectos adversos , Quinazolinas/efectos adversos , República de Corea/epidemiología , Factores de Riesgo , Tailandia/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Gemcitabina
6.
J Med Assoc Thai ; 97(5): 548-53, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-25065096

RESUMEN

OBJECTIVE: To evaluate the outcome and safety of ultrasound-guided percutaneous catheter drainage of exudative pleural effusion. MATERIAL AND METHOD: The present study was a retrospective analysis of 412 pleural effusions from 373 patients that underwent ultrasound-guided small-bore catheter drainage in exudative pleural effusions between 2004 and 2009. RESULTS: The two most common causes for drainage were parapneumonic effusion or empyema (52.2%) and malignant effusion (30.3%), while the remains were trauma, iatrogenic, and others. Overall clinical success rate was 76.5%. The success rate was lower among malignant pleural effusion (p = 0.003). Causes of effusion were the only independent predictors related to success. Only five (1.2%) patients developed complication during the procedure. Seventy-five of 412 effusions (15.8%) developed complication during the period of drainage; the majority were drain blockage (9%) and accidental dislodgment (4.1%). CONCLUSION: Ultrasound-guided small-bore catheter drainage was a safe and efficient procedure for exudative pleural effusions.


Asunto(s)
Tubos Torácicos , Drenaje/instrumentación , Derrame Pleural/cirugía , Ultrasonografía Intervencional , Femenino , Humanos , Masculino , Persona de Mediana Edad , Derrame Pleural/diagnóstico por imagen , Derrame Pleural/etiología , Estudios Retrospectivos , Resultado del Tratamiento
7.
Cureus ; 16(7): e64861, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39026574

RESUMEN

PURPOSE: This study aims to assess the association between admission-corrected serum calcium phosphate (CaPO4) levels and the risks of in-hospital acute kidney injury (AKI) and mortality, hypothesizing a dose-dependent relationship between serum CaPO4 concentrations and the likelihood of developing AKI. METHODS: This large retrospective cohort study analyzed hospitalized adult patients who had serum calcium, phosphate, and albumin levels measured within 24 hours of admission between January 2014 and December 2018. Piecewise regression was employed to identify the optimal CaPO4 cutoff values for predicting in-hospital AKI and mortality. Subsequently, the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the risks of in-hospital AKI and mortality associated with these cutoff values. RESULTS: A total of 2,116 patients were included in the study. The incidence rates of AKI for patients with CaPO4 levels ≤27 and >27 mg2/dL2 were 9.6% and 10.9%, respectively. The bilinear association pattern revealed the lowest risk of AKI at a CaPO4 level of 27 mg2/dL2. Piecewise regression analysis showed that each 1 mg2/dL2 increase in CaPO4 level above the 27 mg2/dL2 cutoff was associated with increased risks of in-hospital AKI and mortality, with OR of 1.048 (95% CI: 1.030-1.065) and 1.048 (95% CI: 1.032-1.065), respectively. CONCLUSION: Our findings indicate a critical relationship between elevated serum CaPO4 levels and increased risks of in-hospital AKI and mortality, with a notable cutoff at CaPO4 >27 mg2/dL2.

8.
Thorac Cancer ; 15(16): 1287-1295, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38666456

RESUMEN

BACKGROUND: Various cutoffs have been used to diagnose computed tomography (CT)-defined low skeletal muscle mass; however, the impact of this variability on predicting physical functional limitations (PFL) remains unclear. In the present study we aimed to evaluate the diagnostic test metrics for predicting PFLs using a fixed cutoff value from previous reports and sought to create a prediction score that incorporated the skeletal muscle index (SMI) and other clinical factors. METHODS: In this cross-sectional study including 237 patients with lung cancer, the SMI was assessed using CT-determined skeletal muscle area at the third lumbar vertebra. Physical function was assessed using the short physical performance battery (SPPB) test, with PFL defined as an SPPB score ≤9. We analyzed the diagnostic metrics of the five previous cutoffs for CT-defined low skeletal muscle mass in predicting PFL. RESULTS: The mean age of participants was 66.0 ± 10.4 years. Out of 237 patients, 158 (66.7%) had PFLs. A significant difference was observed in SMI between individuals with and without PFLs (35.7 cm2/m2 ± 7.8 vs. 39.5 cm2/m2 ± 8.4, p < 0.001). Diagnostic metrics of previous cutoffs in predicting PFL showed suboptimal sensitivity (63.29%-91.77%), specificity (11.39%-50.63%), and area under the receiver operating characteristic curve (AUC) values (0.516-0.592). Age and the SMI were significant predictors of PFL; therefore, a score for predicting PFL (age - SMI + 21) was constructed, which achieved an AUC value of 0.748. CONCLUSION: Fixed cutoffs for CT-defined low skeletal muscle mass may inadequately predict PFLs, potentially overlooking declining physical functions in patients with lung cancer.


Asunto(s)
Neoplasias Pulmonares , Músculo Esquelético , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Anciano , Tomografía Computarizada por Rayos X/métodos , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/fisiopatología , Estudios Transversales , Persona de Mediana Edad , Sarcopenia/diagnóstico por imagen
9.
Ann Am Thorac Soc ; 21(5): 803-813, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38252423

RESUMEN

Rationale: Maternal obstructive sleep apnea-hypopnea (OSAH) is associated with hypertensive disorders of pregnancy (HDP). OSAH treatment with positive airway pressure (PAP) in the general population lowers blood pressure (BP). However, there are limited data on the effects of PAP therapy in maternal OSAH. Objectives: Our primary objective was to assess the feasibility of recruitment to a pilot randomized trial and adherence to PAP therapy for OSAH in women with HDP. Secondary objectives included assessment of PAP effects on 24-h BP, arterial stiffness, and maternal and fetal outcomes. Methods: Women with singleton pregnancies at ⩾12 weeks' gestation and hypertension underwent home level 2 polysomnography; those with mild to moderate OSAH (apnea-hypopnea index ⩾ 5 events/h; women with severe OSAH with apnea-hypopnea index > 30 events/h and oxygen desaturation index > 30 were excluded) were randomized to either PAP or nasal dilator strip (NDS; control) therapy. After PAP education, adherence was monitored online with episodic phone or in-person support by research personnel. Twenty-four-hour BP and arterial stiffness were assessed at baseline and before delivery. Maternal and fetal outcomes were also recorded. Results: Of 105 potentially eligible participants, 67 agreed to undergo screening for OSAH over 38 months; 48 women meeting OSAH inclusion criteria were randomized to PAP (n = 27) or NDS (n = 21) therapy. Of these, 14 PAP (52%) and 13 NDS (62%) participants completed all predelivery measurements, with lack of completion due to urgent delivery (19% in the PAP group, 14% in the NDS group), PAP intolerance at initiation (19%), or other factors. Mean PAP use was 3.1 ± 2.5 h/night, with use ⩾4 h/night on 38.4 ± 33.7% of nights during 9.6 ± 4.0 weeks of treatment. BP was controlled within the target range in most participants. There were no differences in mean change in 24-hour BP or arterial stiffness measurements or in adverse maternal and fetal outcomes between the PAP and NDS groups in either intention-to-treat or per-protocol analyses. Conclusions: PAP adherence was suboptimal in this HDP cohort despite education and troubleshooting. Further work is required to identify optimal OSAH treatment strategies during pregnancy. Clinical trial registered with www.clinicaltrials.gov (NCT03309826).


Asunto(s)
Presión de las Vías Aéreas Positiva Contínua , Hipertensión Inducida en el Embarazo , Polisomnografía , Apnea Obstructiva del Sueño , Humanos , Femenino , Embarazo , Apnea Obstructiva del Sueño/terapia , Apnea Obstructiva del Sueño/fisiopatología , Proyectos Piloto , Adulto , Hipertensión Inducida en el Embarazo/terapia , Presión de las Vías Aéreas Positiva Contínua/métodos , Prueba de Estudio Conceptual , Presión Sanguínea/fisiología , Rigidez Vascular/fisiología
10.
Front Public Health ; 10: 965808, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36311589

RESUMEN

Objective: Universal health coverage can decrease the magnitude of the individual patient's financial burden of chronic kidney disease (CKD), but the residual financial hardship from the patients' perspective has not been well-studied in low and middle-income countries (LMICs). This study aimed to evaluate the residual financial burden in patients with CKD stage 3 to dialysis in the "PD First Policy" under Universal Coverage Scheme (UCS) in Thailand. Methods: This multicenter nationwide cross-sectional study in Thailand enrolled 1,224 patients with pre-dialysis CKD, hemodialysis (HD), and peritoneal dialysis (PD) covered by UCS and other health schemes for employees and civil servants. We interviewed patients to estimate the proportion with catastrophic health expenditure (CHE) and medical impoverishment. The risk factors associated with CHE were analyzed by multivariable logistic regression. Results: Under UCS, the total out-of-pocket expenditure in HD was over two times higher than PD and nearly six times higher than CKD stages 3-4. HD suffered significantly more CHE and medical impoverishment than PD and pre-dialysis CKD [CHE: 8.5, 9.3, 19.5, 50.0% (p < 0.001) and medical impoverishment: 8.0, 3.1, 11.5, 31.6% (p < 0.001) for CKD Stages 3-4, Stage 5, PD, and HD, respectively]. In the poorest quintile of UCS, medical impoverishment was present in all HD and two-thirds of PD patients. Travel cost was the main driver of CHE in HD. In UCS, the adjusted risk of CHE increased in PD and HD (OR: 3.5 and 16.3, respectively) compared to CKD stage 3. Conclusions: Despite universal coverage, the residual financial burden remained high in patients with kidney failure. CHE was considerably lower in PD than HD, although the rates remained alarmingly high in the poor. The "PD First' program" could serve as a model for other LMICs. However, strategies to minimize financial distress should be further developed, especially for the poor.


Asunto(s)
Diálisis Peritoneal , Insuficiencia Renal Crónica , Humanos , Cobertura Universal del Seguro de Salud , Tailandia , Estudios Transversales , Insuficiencia Renal Crónica/terapia , Políticas
11.
Lung Cancer Manag ; 8(3): LMT15, 2019 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-31807143

RESUMEN

AIM: The current study evaluated the efficacy and tolerability of second-line afatinib in patients with EGFR mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC) following chemotherapy. PATIENTS & METHODS: In this open-label, single-arm Phase IV study, patients with EGFRm+ (Del19/L858R) NSCLC who had progressed following platinum-based chemotherapy received afatinib (starting dose 40 mg/day). The primary end point was confirmed objective response. RESULTS: 60 patients received afatinib for a median duration of 11.5 months. 50% of patients had a confirmed objective response, of median duration 13.8 months. Median progression-free survival was 10.9 months. The most common treatment-related adverse events were diarrhea (72%), rash (28%) and paronychia (23%). CONCLUSION: Our data support the use of afatinib (40 mg/day) as an effective and well-tolerated second-line treatment in EGFRm+ NSCLC.

12.
J Thorac Oncol ; 14(7): 1255-1265, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30851442

RESUMEN

INTRODUCTION: In an earlier report of the ASCEND-8 study (open-label, phase I, three-arm study, treatment-naive patients and pre-treated patients with advanced/metastatic NSCLC), it was shown that ceritinib 450 mg with food had comparable exposure and better gastrointestinal tolerability than 750-mg fasted. METHODS: Here, we report efficacy and updated safety data from primary efficacy analysis of the ASCEND-8 study. Key secondary endpoints were overall response rate and duration of response, assessed by blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumors 1.1. RESULTS: In total, 306 patients were randomized to ceritinib 450-mg fed (n = 108) or 600-mg fed (n = 87) or 750-mg fasted (n = 111), of which 304 patients were included in safety analysis and 198 treatment-naive patients (ALK receptor tyrosine kinase [ALK]-positive by immunohistochemistry) were included in the efficacy analysis (450-mg fed [n = 73], 600-mg fed [n = 51], and 750-mg fasted [n = 74]). The BIRC-assessed overall response rate was 78.1% (95% confidence interval [CI]: 66.9-86.9), 72.5% (95% CI: 58.3-84.1), and 75.7% (95% CI: 64.3-84.9), respectively; and the median duration of response (months) by BIRC was not estimable (NE) (95% CI: 11.2-NE), 20.7 (95% CI: 15.8-NE), and 15.4 (95% CI: 8.3-NE), respectively. Based on the safety analysis (n = 304), the 450-mg fed arm showed the highest median relative dose intensity (100% versus 78.5% versus 83.7%), lowest proportion of patients with dose reductions (24.1% versus 65.1% versus 60.9%), and lowest proportion of patients with gastrointestinal toxicities (75.9% versus 82.6% versus 91.8%). CONCLUSION: Ceritinib at a dose of 450 mg with food compared to 750-mg fasted showed consistent efficacy and less gastrointestinal toxicity.


Asunto(s)
Quinasa de Linfoma Anaplásico/genética , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Ayuno , Alimentos , Neoplasias Pulmonares/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Neoplasias Óseas/secundario , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Reordenamiento Génico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Pronóstico , Criterios de Evaluación de Respuesta en Tumores Sólidos , Adulto Joven
13.
J Med Imaging Radiat Oncol ; 62(5): 619-624, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29624885

RESUMEN

INTRODUCTION: Pleural procedures are performed to prove the diagnosis of pleural effusion. This study was to assess the incidence and outcome of pleural procedure-related tumour seeding in lung cancer with malignant pleural effusion, and to review the characteristics of the implanted tumours on computed tomography (CT) images. METHODS: From January 2008 to December 2010, 165 patients with the diagnosis of lung cancer with malignant pleural effusion, who underwent at least one pleural procedure and had follow-up CT, were included. Two radiologists retrospectively reviewed the presence of implanted tumours and their manifestations on CT images. The incidence of tumour seeding, the time to tumour seeding, and hazard ratios for death associated with the procedures and presence of tumour seeding were evaluated. Multivariable logistic regression analysis was used to identify variables that were independently associated with procedure-related tumour seeding. RESULTS: The incidence of procedure-related tumour seeding was 22.4%. Conventional intercostal drainage (ICD) was the independent predictor of tumour seeding. Patients with a history of ICD rapidly developed implanted tumours (P = 0.0319). The estimated mean time of tumour seeding was 2.9 months. There was an increased risk of death with the presence of tumour seeding (HR: 3.35, 95% CI: 1.87-6.01). The majority of CT features showed ill-defined margins with heterogeneous enhancement. CONCLUSION: Pleural procedure-related tumour seeding in lung cancer with malignant pleural effusion is common. There was a significantly increased risk of death with the presence of tumour seeding. The majority of the CT features in implanted tumours were ill-defined margins with heterogeneous enhancement.


Asunto(s)
Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Siembra Neoplásica , Derrame Pleural Maligno/diagnóstico por imagen , Derrame Pleural Maligno/patología , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Medios de Contraste , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Toracocentesis
14.
Patient ; 11(1): 131-141, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29178024

RESUMEN

INTRODUCTION: In LUX-Lung 3 and LUX-Lung 6, afatinib significantly improved progression-free survival (PFS) versus chemotherapy in patients with tumors harboring common epidermal growth factor receptor (EGFR) mutations (Del19/L858R) and significantly improved overall survival (OS) in patients with tumors harboring Del19 mutations. Patient-reported outcomes stratified by EGFR mutation type are reported. PATIENTS AND METHODS: Lung cancer symptoms and health-related quality of life (QoL) were assessed every 21 days until progression using the EORTC Quality of Life Core Questionnaire C30 and its lung cancer-specific module, LC13. Analyses of cough, dyspnea, and pain were prespecified and included analysis of percentage of patients who improved on therapy, time to deterioration of symptoms, and change over time. Global health status (GHS)/QoL was also assessed. Analyses were conducted for all patients with tumors harboring Del19 or L858R mutations and were exploratory. RESULTS: Compared with chemotherapy, afatinib more commonly improved symptoms of, delayed time to deterioration for, and was associated with better mean scores over time for cough and dyspnea in patients with Del19 or L858R mutations. All three prespecified analyses of pain showed a trend favoring afatinib over chemotherapy. In both Del19 and L858R mutations, afatinib was also associated with improvements in GHS/QoL. Longitudinal analyses demonstrated statistically significant improvements in GHS/QoL for afatinib over chemotherapy for patients with tumors harboring Del19 mutations or L858R mutations. CONCLUSIONS: These exploratory analyses suggest first-line afatinib improved lung cancer-related symptoms and GHS/QoL compared with chemotherapy in patients with non-small-cell lung cancer with tumors harboring common EGFR mutations, with benefits in both Del19 and L858R patients. When considered with OS (Del19 patients only) and PFS benefits, these findings substantiate the value of using afatinib over chemotherapy in these patient groups.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Quinazolinas/uso terapéutico , Afatinib , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Femenino , Estado de Salud , Humanos , Neoplasias Pulmonares/fisiopatología , Masculino , Medición de Resultados Informados por el Paciente , Polimorfismo de Nucleótido Simple , Calidad de Vida , Análisis de Supervivencia
15.
Clin Lung Cancer ; 19(4): e465-e479, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29653820

RESUMEN

BACKGROUND: Afatinib is approved in the US, Europe, and several other regions for first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Treatment-naive patients with advanced EGFRm+ NSCLC were randomized to afatinib (40 mg/d) versus cisplatin/pemetrexed (LUX-Lung 3 [LL3]) or cisplatin/gemcitabine (LUX-Lung 6 [LL6]), or versus gefitinib (250 mg/d; LUX-Lung 7 [LL7]). We report subgroup analyses according to age, including 65 years or older versus younger than 65 years (preplanned; LL3/LL6) and additional cutoffs up to 75 years and older (exploratory; LL7). Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. RESULTS: Among the 134 of 345 (39%) and 86 of 364 (24%) patients aged 65 years and older in LL3 and LL6, median PFS was improved with afatinib versus chemotherapy (LL3: hazard ratio [HR], 0.64 [95% confidence interval (CI), 0.39-1.03]; LL6: HR, 0.16 [95% CI, 0.07-0.39]). Afatinib significantly improved OS versus chemotherapy in elderly patients with Del19+ NSCLC in LL3 (HR, 0.39 [95% CI, 0.19-0.80]). Among the 40 of 319 patients (13%) aged 75 years or older in LL7, median PFS (HR, 0.69 [95% CI, 0.33-1.44]) favored afatinib, consistent with the overall population. Afatinib-associated AEs in older patients were consistent with the overall populations. CONCLUSIONS: Subgroup analyses of the LL3, LL6, and LL7 trials show that afatinib is an effective and tolerable treatment for patients with EGFRm+ NSCLC, independent of age.


Asunto(s)
Afatinib/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Receptores ErbB/genética , Femenino , Gefitinib/uso terapéutico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Mutación , Pemetrexed/uso terapéutico , Supervivencia sin Progresión , Gemcitabina
16.
Saf Health Work ; 8(3): 250-257, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28951801

RESUMEN

BACKGROUND: Tasks involved in traditional charcoal production expose workers to various levels of charcoal dust and wood smoke. This study aimed to identify specific tasks influencing lung function and respiratory symptoms. METHODS: Interviews, direct observation, and task/symptom checklists were used to collect data from 50 charcoal-production workers on 3 nonwork days followed by 11 workdays. The peak expiratory flow rate (PEFR) was measured four times per day. RESULTS: The PEFR was reduced and the prevalence of respiratory symptoms increased over the first 6-7 workdays. The PEFR increased until evening on nonwork days but not on workdays. Loading the kiln and collecting charcoal from within the kiln markedly reduced the PEFR and increased the odds of respiratory symptoms. CONCLUSION: Tasks involving entry into the kiln were strongly associated with a short-term drop in the PEFR and the occurrence of respiratory symptoms, suggesting a need for the use of protective equipment and/or the operation of an effective kiln ventilation system.

17.
J Thorac Oncol ; 10(6): 883-9, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25933111

RESUMEN

INTRODUCTION: In the phase III, LUX-Lung 6 trial, afatinib prolonged progression-free survival (PFS) versus cisplatin/gemcitabine in Asian patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). This article provides detailed assessments of patient-reported outcomes (PROs), a LUX-Lung 6 secondary end point, and explores the relationship between PFS and health-related quality of life (QoL) in these patients. METHODS: Patients (n = 364) were randomized (2:1) to oral afatinib (40 mg/day) or up to six cycles of cisplatin/gemcitabine (21-day cycle; cisplatin 75 mg/m(2) [d1]; gemcitabine 1000 mg/m(2) [d1,8]). QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and its lung cancer-specific module. The relationship between PFS (investigator assessment and independent review) and QoL was evaluated using analysis of covariance and a longitudinal model. RESULTS: More patients treated with afatinib versus cisplatin/gemcitabine showed improvements in global health status/QoL (p < 0.0001) and physical (p < 0.0001), role (p = 0.013), and social (p < 0.001) functioning scales. Delayed symptom deterioration and better QoL over time was also observed with afatinib. QoL measured before tumor assessment was considerably poorer for patients with progression than those without progression, with significant differences in mean scores at multiple assessment time points. Results from the longitudinal analysis consistently demonstrated a significant negative impact of progression on QoL (p < 0.0001). CONCLUSION: Afatinib improved PFS and PROs versus chemotherapy in EGFR mutation-positive NSCLC patients. Progression was associated with statistically significant worsening in QoL measured before tumor assessment, underscoring the value of PFS as a clinically relevant end point.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pueblo Asiatico/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/uso terapéutico , Adulto , Afatinib , Anciano , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Calidad de Vida , Resultado del Tratamiento , Gemcitabina
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