RESUMEN
BACKGROUND: Adjuvant oral uracil-tegafur (UFT) has led to significantly longer postoperative survival among patients with non-small-cell lung cancer (NSCLC). Gemcitabine (GEM) monotherapy is also reportedly effective for NSCLC and has minor adverse events (AEs). This study compared the efficacy of GEM- versus UFT-based adjuvant regimens in patients with completely resected pathological stage (p-stage) IB-IIIA NSCLC. PATIENTS AND METHODS: Patients with completely resected p-stage IB-IIIA NSCLC were randomly assigned to GEM or UFT. The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and AEs. RESULTS: We assigned 305 patients to the GEM group and 303 to the UFT group. Baseline factors were balanced between the arms. Of the 608 patients, 293 (48.1%) had p-stage IB disease, 195 (32.0%) had p-stage II disease and 121 (19.9%) had p-stage IIIA disease. AEs were generally mild in both groups, and only one death occurred, in the GEM group. After a median follow-up of 6.8 years, the two groups did not significantly differ in survival: 5 year OS rates were GEM: 70.0%, UFT: 68.8% (hazard ratio 0.948; 95% confidence interval 0.73-1.23; P = 0.69). CONCLUSION: Although GEM-based adjuvant therapy for patients with completely resected stage IB-IIIA NSCLC was associated with acceptable toxicity, it did not provide longer OS than did UFT.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Desoxicitidina/análogos & derivados , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Tegafur , Uracilo/uso terapéutico , GemcitabinaRESUMEN
OBJECTIVE: Concurrent chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer. In the current aging society, the establishment of an ideal treatment strategy for locally advanced non-small cell lung cancer in the elderly is warranted. To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. PURPOSE: To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. METHODS: This multicenter, phase II study included patients with physiologically or medically unresectable stage I-III NSCLC, who were ≥70 years old. The patients received carboplatin (AUC 2) and vinorelbine (15 mg/m2) both on day 1, 8, 22 and 29 concurrently with radiotherapy (2.0 Gy/day, 30 fractions, total 60 Gy). The primary endpoint was the objective response rate. The secondary endpoints were the progression-free survival, overall survival and the incidence of adverse events. RESULTS: 50 patients were accrued (42 men and 8 women). The median age was 77 years (range, 70-89 years) and the clinical stage was I/II/III in 3/7/40, respectively. Forty-seven patients completed the planned treatment. The response was complete remission in 4, partial response in 31, stable disease in 12 and progressive disease in 3, giving an objective response rate of 70% (95% confidence interval: 55.4-82.1). Frequent high Grade 3 or higher adverse events were hematologic, but no treatment deaths were noted. The median and 2-year progression-free survival were 8.4 months and 21.1% (95% confidence interval: 9.5-32.7%), respectively, and the median and 2-year overall survival were 15.4 months and 41.1% (95% confidence interval: 27.0-55.2), respectively. CONCLUSION: Concurrent chemoradiotherapy with carboplatin and vinorelbine showed an acceptable objective response rate and safety in elderly patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Neoplasias Pulmonares/terapia , Vinorelbina/uso terapéutico , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Dosificación Radioterapéutica , Inducción de Remisión , Análisis de SupervivenciaRESUMEN
It is not clear whether sequential chemotherapy can be performed immediately in patients with p-stage I non-small cell lung cancer recurring during a 2-year period of daily oral administration with tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. Patients receiving chemotherapy within 1 month after the discontinuation of UFT (n = 10) (five cases with aggressive recurrent tumors) had the increased risk of grade 4 neutropenia, but the overall survival was not inferior to that in patients who received chemotherapy beginning more than 1 month (n = 11). We could perform sequential chemotherapy immediately while paying attention to grade 4 neutropenia.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neutropenia , Periodo Posoperatorio , Estudios Retrospectivos , Análisis de Supervivencia , Tegafur/administración & dosificación , Tegafur/efectos adversos , Resultado del Tratamiento , Uracilo/administración & dosificación , Uracilo/efectos adversosRESUMEN
Determinants of interindividual variability in erlotinib pharmacokinetics (PK) and adverse events remain to be elucidated. This study with 50 Japanese non-small-cell lung cancer patients treated with oral erlotinib at a standard dose of 150 mg aimed to investigate whether genetic polymorphisms affect erlotinib PK and adverse events. Single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP1A1, CYP1A2, CYP2D6, CYP3A4, CYP3A5, UGT1A1, UGT2B7, GSTM1, and GSTT1) or efflux transporters (ABCB1, and ABCG2) were analyzed as covariates in a population PK model. The ABCB1 1236C>T (rs1128503) polymorphism, not ABCB1*2 haplotype (1236TT-2677TT-3455TT, rs1128503 TT-rs2032582 TT-rs1045642 TT), was a significant covariate for the apparent clearance (CL/F), with the TT genotype showing a 29.4% decrease in CL/F as compared with the CC and the CT genotypes. A marginally higher incidence of adverse events (mainly skin rash) was observed in the TT genotype group; however, patients with high plasma erlotinib exposure did not always experience skin rash. None of the other SNPs affected PK or adverse events. The ABCB1 genotype is a potential predictor for erlotinib adverse events. Erlotinib might be used with careful monitoring of adverse events in patients with ABCB1 polymorphic variants.
Asunto(s)
Antineoplásicos/farmacocinética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Clorhidrato de Erlotinib/farmacocinética , Neoplasias Pulmonares/metabolismo , Modelos Biológicos , Polimorfismo de Nucleótido Simple , Transportadoras de Casetes de Unión a ATP/genética , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Sistema Enzimático del Citocromo P-450/genética , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Clorhidrato de Erlotinib/efectos adversos , Clorhidrato de Erlotinib/uso terapéutico , Femenino , Glucuronosiltransferasa/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Estudios ProspectivosRESUMEN
We retrospectively evaluated whether preoperative percutaneous transthoracic needle biopsy (PTNB) affected the incidence of pleural recurrence in pathological stage I lung cancer patients. Pleural recurrence occurred in pure solid nodule (PSN) cases but not in ground-glass nodule cases, as evaluated using thin-section computed tomographic imaging. When the cases were restricted to sub-pleural PSN, the incidence of recurrence tended to be higher in a PTNB group (63 patients diagnosed by PTNB) than in a non-PTNB group (86 patients diagnosed by transbronchial biopsy or intraoperative diagnosis) (25% vs. 4%, p =.050). PTNB should not be performed in patients with a sub-pleural PSN.
Asunto(s)
Biopsia con Aguja/efectos adversos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pleurales/diagnóstico , Nódulo Pulmonar Solitario/diagnóstico , Anciano , Anciano de 80 o más Años , Biopsia con Aguja/métodos , Terapia Combinada , Femenino , Humanos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Cuidados Preoperatorios , Estudios Retrospectivos , Riesgo , Nódulo Pulmonar Solitario/cirugía , Nódulo Pulmonar Solitario/terapia , Tomografía Computarizada por Rayos X , Carga TumoralRESUMEN
We retrospectively evaluated whether the ratio KL-6 to SLX in serum (K/S ratio) before chemotherapy was a predictor for the occurrence of drug-induced interstitial lung disease (D-ILD) in lung cancer patients with idiopathic interstitial pneumonias (IIPs). D-ILD occurred in 8 of 20 IIPs-positive cases and in 14 of 100 IIPs-negative cases (40 vs. 14%, p = .015). In IIPs-positive cases, the high K/S ratio (>20) before first-line chemotherapy had a tendency to increase the risk of D-ILD (p = .085). Serum K/S ratio may be a useful predictor for the occurrence of D-ILD in lung cancer patients with IIPs.
Asunto(s)
Endonucleasas/metabolismo , Neumonías Intersticiales Idiopáticas/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , Mucina-1/metabolismo , Anciano , Endodesoxirribonucleasas , Endonucleasas/sangre , Femenino , Humanos , Masculino , Mucina-1/sangre , Estudios RetrospectivosRESUMEN
BACKGROUND: With the recent widespread use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), there have been occasional reports on complications associated with its use. Previous reviews on EBUS-TBNA have been limited to studies by skilled operators, thus the results may not always be applicable to recent clinical practice. To assess the safety of EBUS-TBNA for the staging and diagnosis of lung cancer in Japan, a nationwide survey on its current usage status and complications associated with its use was conducted by the Japan Society for Respiratory Endoscopy (JSRE). METHODS: A questionnaire about EBUS-TBNA performed between January 2011 and June 2012 was mailed to 520 JSRE-accredited facilities. RESULTS: Responses were obtained from 455 facilities (87.5%). During the study period, EBUS-TBNA was performed in 7,345 cases in 210 facilities (46.2%) using a convex probe ultrasound bronchoscope, for 6,836 mediastinal and hilar lesions and 275 lung parenchymal lesions. Ninety complications occurred in 32 facilities. The complication rate was 1.23% (95% confidence interval, 0.97%-1.48%), with hemorrhage being the most frequent complication (50 cases, 0.68%). Infectious complications developed in 14 cases (0.19%) (Mediastinitis, 7; pneumonia, 4; pericarditis, 1; cyst infection, 1; and sepsis, 1). Pneumothorax developed in 2 cases (0.03%), one of which required tube drainage. Regarding the outcome of the cases with complications, prolonged hospitalization was observed in 14 cases, life-threatening conditions in 4, and death in 1 (severe cerebral infarction) (mortality rate, 0.01%). Breakage of the ultrasound bronchoscope occurred in 98 cases (1.33%) in 67 facilities (31.9%), and that of the puncture needle in 15 cases (0.20%) in 8 facilities (3.8%). CONCLUSIONS: Although the complication rate associated with EBUS-TBNA was found to be low, severe complications, including infectious complications, were observed, and the incidence of device breakage was high. Since the use of EBUS-TBNA is rapidly expanding in Japan, an educational program for its safe performance should be immediately established.
Asunto(s)
Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/mortalidad , Hemorragia/mortalidad , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neumotórax/mortalidad , Complicaciones Posoperatorias/mortalidad , Infección de la Herida Quirúrgica/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Recolección de Datos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/estadística & datos numéricos , Femenino , Humanos , Incidencia , Japón/epidemiología , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
OBJECTIVE: It is important to identify optimal regimens of cisplatin-based, third-generation chemotherapy and thoracic radiotherapy for patients with unresectable, Stage III, non-small cell lung cancer. METHODS: Patients with unresectable, Stage III non-small cell lung cancer were treated with the following regimen: cisplatin 80 mg/m(2) on days 1 and 29, with irinotecan 60 mg/m(2) on days 1, 8, 15, 29, 36, and 43 and 30 mg/m(2) on days 57, 64, 71, 78, 85 and 92. Thoracic radiotherapy was started on day 57 at 2 Gy/day (total 60 Gy). RESULTS: From February 1998 to January 1999, 68 patients were enrolled. Grade 3/4 toxicities during induction chemotherapy primarily included neutropenia (73.5%) and diarrhea (20.6%), while Grade 3/4 toxicities during concomitant thoracic radiotherapy with irinotecan consisted of neutropenia (18.4%), esophagitis (4.1%) and hypoxia (6.5%). There was one treatment-related death due to radiation pneumonitis. The response rate was 64.7% (95% confidence interval, 52.2-75.9%). The median survival time was 16.5 (95% confidence interval, 12.6-19.8) months. The 1- and 2 year survival rates were 65.8% (95% confidence interval, 54.4-77.1%) and 32.9% (95% confidence interval, 21.6-44.1%), respectively. Overall, only 36 (56%) completed both the scheduled chemotherapy and thoracic radiotherapy. CONCLUSIONS: Induction chemotherapy with cisplatin plus irinotecan followed by low-dose irinotecan and concomitant thoracic radiotherapy was feasible according to the prespecified decision criteria in this study for patients with unresectable Stage III non-small cell lung cancer. We did not decide to select this regimen for further investigations because approximately half of the patients completed the scheduled treatment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Anciano , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Esquema de Medicación , Esofagitis/epidemiología , Femenino , Humanos , Incidencia , Irinotecán , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neumonía/epidemiología , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Radioterapia Adyuvante , Inducción de Remisión , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The safety and efficacy of transbronchial microwave ablation (TMA) therapy in patients with malignant central airway obstruction (CAO) with respiratory failure remains unclear. METHODS: A total of 38 patients with advanced non-small cell lung cancer (NSCLC) or lung metastases with malignant endoluminal obstruction received TMA therapy under moderate sedation and high fractions of inspired oxygen (FiO2). The success rate of airway patency restoration, complication rate, and overall survival time (OS) from the initiation of TMA therapy were compared in the following two groups of patients with malignant CAO patients: the group with respiratory failure (PaO2/FiO2 ≤ 300) (RF group, n = 10) and the group without respiratory failure (PaO2/FiO2 > 300) (non-RF group, n = 28) at the time of the TMA therapy. RESULTS: Both the RF group and non-RF group received a median of two sessions of TMA. There was no significant difference in the percentage of patients who showed restored airway patency after the first session of TMA (90% vs. 96%), in the complication rate of TMA therapy (10% vs. 11%), or in the OS (7.1 months vs. 9.1 months) between the RF group and the non-RF group. Multivariate analysis identified no significant association between TMA therapy and the risk of death in malignant CAO patients with respiratory failure (p = 0.196). CONCLUSION: TMA therapy under moderate sedation was well tolerated and effective in patients with malignant CAO, including those with respiratory failure.
Asunto(s)
Obstrucción de las Vías Aéreas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Sedación Consciente/métodos , Neoplasias Pulmonares/cirugía , Microondas/uso terapéutico , Ablación por Radiofrecuencia/mortalidad , Insuficiencia Respiratoria/cirugía , Anciano , Anciano de 80 o más Años , Obstrucción de las Vías Aéreas/etiología , Broncoscopía , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Insuficiencia Respiratoria/complicaciones , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: In EGFR-mutant NSCLC patients with oligo-progression disease (oligo-PD) after the EGFR-TKI failure, additional local ablative therapy (LAT) including stereotactic ablative radiotherapy reportedly extends the duration of the current EGFR-TKI and prolongs survival times. In clinical practice, however, all the patients cannot receive LAT for oligo-PD. METHODS: We retrospectively evaluated the efficacy and tolerability of additional bevacizumab as an alternative to LAT for oligo-PD after the EGFR-TKI failure in previously treated lung adenocarcinoma patients (median number of previous therapies, 2 regimens). Oligo-PD was defined as a situation in which disease progression has occurred in less than 5 anatomical sites after EGFR-TKI that has achieved at least stable disease. RESULTS: During a median 29.6-month follow-up period from the initiation of EGFR-TKI, 9 patients developed oligo-PD. One patient underwent LAT, but other 8 patients did not because of a few micro-metastatic lesions (nâ¯=â¯2), meningitis (nâ¯=â¯1), no indication of pleurodesis (nâ¯=â¯1), patient refusal (nâ¯=â¯2) or oligo-PD in the LAT treated sites (nâ¯=â¯3). Additional bevacizumab with continuation of the current EGFR-TKI had a disease control rate of 100% and a median time of progression-free survival from additional bevacizumab until another PD was 8.8 months. The reason for the discontinuation was because of another PD (nâ¯=â¯6) or treatment-related adverse events (nâ¯=â¯3). Four patients received sequential therapy and overall survival from additional bevacizumab was 10.1 months. CONCLUSIONS: Additional bevacizumab could be useful for EGFR-mutant adenocarcinoma patients with oligo-PD after the EGFR-TKI failure.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Recurrencia Local de Neoplasia/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioterapia Adyuvante , Progresión de la Enfermedad , Resistencia a Antineoplásicos/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Estudios de Factibilidad , Femenino , Humanos , Pulmón/patología , Pulmón/cirugía , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Neumonectomía , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios RetrospectivosRESUMEN
We reported that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor re-administration (TKI-R) might be salvage therapy in patients with advanced non-small cell lung cancer after recovery from EGFR-TKI-induced interstitial lung disease (ILD). Here we retrospectively evaluated whether chemotherapy re-administration (CT-R) was effective in patients after chemotherapy-induced ILD. After providing their informed consent due to the risk of severe ILD, five patients received CT-R and six received TKI-R with oral administration of 0.5 mg/kg prednisolone. The overall survival (OS) from the occurrence of drug-induced ILD was shorter in CT-R cases than that in TKI-R cases (7.3 months vs. 25.4 months, p=0.003). The median duration of OS, however, was 7.3 months in cases with CT-R and 1.9 months in cases without CT-R. Multivariate analysis showed that CT-R as well as TKI-R tended to reduce the risk of mortality. CT-R might be salvage therapy in such patients, although the benefit of CT-R was smaller than that of TKI-R.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Receptores ErbB/genética , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Receptores ErbB/antagonistas & inhibidores , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Mutación , Inhibidores de Proteínas Quinasas/administración & dosificación , Estudios Retrospectivos , Terapia RecuperativaRESUMEN
We report 8 rare cases of primary lung cancer which showed a thin-walled cavity on chest X-ray and CT. We analyzed 8 cases (7 men, 1 woman) of primary lung cancer with thin-walled cavities admitted to our hospital between 1995 and 2006. The subjects were aged between 45 and 84 years of age (median: 72 years old). The reason for detection was treatment for tuberculosis in 1 case, ileus owing to metastasis to the small intestine in 1 case and tension pnumathorax 1 case, while 5 cases had abnormal chest x-ray film shadows without symptoms. Histologically, there were 5 cases of adenocarcinoma, 2 of squamous cell carcinoma, and 1 of adenosquamous cell carcinoma. Though various reports on the mechanism of the development of thin-walled cavity formation have been made, we suggest that it mainly develops by a check-valve mechanism, based on evaluation of the clinical course.
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Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Carcinoma Adenoescamoso/diagnóstico por imagen , Carcinoma Adenoescamoso/patología , Carcinoma de Células Escamosas/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Adenocarcinoma/etiología , Anciano , Anciano de 80 o más Años , Carcinoma Adenoescamoso/etiología , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Neoplasias Pulmonares/etiología , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: Several non-small cell lung cancer (NSCLC) cases of successful rechallenge with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after recovery from gefitinib or erlotinib-induced interstitial lung disease (ILD) have been reported, but it is not clear whether the rechallenge affects the outcome. METHODS: We retrospectively evaluated the difference in the outcome between advanced NCLC patients with active EGFR mutations who received EGFR-TKI rechallenge after recovery from EGFR-TKI-induced ILD and those who did not. RESULTS: EGFR-TKI-induced ILD occurred in 11 (10%) of 110 patients receiving gefitinib, five (7%) of 73 patients receiving erlotinib and one (8%) of 13 patients receiving afatinib. Diffuse alveolar damage pattern ILD was observed in six cases, four of which had chemotherapy-related death. Five of 13 patients who had recovered from ILD received EGFR-TKI rechallenge with concurrent oral administration of prednisolone 0.5 mg/kg after the strict informed consent of the risk for the recurrence of severe ILD. All of the five patients achieved a partial response. The median overall survival from the occurrence of EGFR-TKI-induced ILD was longer in patients with EGFR-TKI rechallenge than that in patients without (15.5 vs. 3.5 months, p = 0.029). The adverse events of EGFR-TKI rechallenge were tolerable, but one case receiving EGFR-TKI rechallenge with the suspected drug exhibited the recurrence of grade 3 ILD after the discontinuation of prednisolone. CONCLUSIONS: EGFR-TKI rechallenge with concurrent prednisolone therapy might be salvage therapy in advanced NSCLC patients with active EGFR mutations after recovery from EGFR-TKI-induced ILD.
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Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Enfermedades Pulmonares Intersticiales/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Clorhidrato de Erlotinib/efectos adversos , Clorhidrato de Erlotinib/uso terapéutico , Femenino , Gefitinib , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/genética , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Mutación/genética , Prednisolona/uso terapéutico , Quinazolinas/efectos adversos , Quinazolinas/uso terapéutico , Estudios Retrospectivos , Terapia Recuperativa/métodos , Análisis de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: Various polymorphisms have been detected in the UDP-glucuronosyltransferase 1A ( UGT1A ) gene, and UGT1A1 *28 and UGT1A1 *6 have important effects on the pharmacokinetics of irinotecan and the risk of severe toxicities during irinotecan therapy. This study was conducted to determine the maximum tolerated dose (MTD) of irinotecan chemotherapy according to the UGT1A1 genotype in previously treated lung cancer patients with the UGT1A1 *28 or UGT1A1 *6 polymorphism. METHODS: The eligibility criteria were as follows: lung cancer patients that had previously been treated with anticancer agents other than irinotecan, possessed the UGT1A1 *28 or UGT1A1 *6 polymorphism (group A included *28/*28, *6/*6, and *28/*6, and group B included *28 /- and *6 /-), were aged ≤75 years old, had a performance score of 0-1, and exhibited adequate bone marrow function. The patients were scheduled to receive irinotecan on days 1, 8, 15, 22, 29, and 36. RESULTS: Four patients were enrolled in this trial. Two patients were determined to be ineligible. The remaining two patients, who belonged to group B, received an initial irinotecan dose of 60 mg/m2 , but did not complete the planned treatment because of diarrhea and leukopenia. Thus, in group B patients, 60 mg/m2 was considered to be the MTD of irinotecan. The study was terminated in group A because of poor case recruitment. CONCLUSIONS: The MTD of irinotecan for previously treated lung cancer patients that are heterozygous for the UGT1A1 * 28 or UGT1A1 * 6 gene polymorphism is 60 mg/m2 .
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Antineoplásicos Fitogénicos/administración & dosificación , Camptotecina/análogos & derivados , Glucuronosiltransferasa/genética , Neoplasias Pulmonares/tratamiento farmacológico , Polimorfismo de Nucleótido Simple , Anciano , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Esquema de Medicación , Femenino , Humanos , Irinotecán , Neoplasias Pulmonares/genética , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Amrubicin is a novel synthetic 9-aminoanthracycline derivative and is converted enzymatically to its C-13 hydroxy metabolite, amrubicinol, whose cytotoxic activity is 10-100 times that of amrubicin. We aimed to determine the maximum tolerated dose (MTD) of amrubicin and to characterize the pharmacokinetics of amrubicin and amrubicinol in previously treated patients with refractory or relapsed lung cancer. The 15 patients were treated with amrubicin intravenously at doses of 30, 35, or 40 mg/m(2) on three consecutive days every 3 weeks for a total of 43 courses. Neutropenia was the major toxicity (grade 4, 67%). The MTD was 40 mg/m(2), with the specific dose-limiting toxicities being grade 4 neutropenia persisting for >4 days, febrile neutropenia, or grade 3 arrhythmia in the three patients treated at this dose. A patient with non-small-cell lung cancer showed a partial response, and ten individuals experienced a stable disease. The area under the plasma concentration versus time curve (AUC) for amrubicin and that for amrubicinol increased with amrubicin dose. The amrubicin AUC was significantly correlated with the amrubicinol AUC. The recommended phase II dose of amrubicin for patients with lung cancer refractory to standard chemotherapy is thus 35 mg/m(2) once a day for three consecutive days every 3 weeks.
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Antraciclinas/farmacocinética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Anciano , Antraciclinas/administración & dosificación , Antraciclinas/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Área Bajo la Curva , Fibrilación Atrial/inducido químicamente , Fibrilación Atrial/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Células Pequeñas/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Disopiramida/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Disnea/inducido químicamente , Disnea/tratamiento farmacológico , Femenino , Semivida , Humanos , Hipoxia/inducido químicamente , Hipoxia/tratamiento farmacológico , Infusiones Intravenosas , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neutropenia/inducido químicamente , Neutropenia/terapia , Transfusión de Plaquetas , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Esteroides/uso terapéutico , Trombocitopenia/inducido químicamente , Trombocitopenia/terapiaRESUMEN
BACKGROUND: Whether a full dosage of afatinib is tolerable and effective for elderly or low performance status (PS) patients with advanced refractory non-small-cell lung cancer (NSCLC) is unclear. METHODS: We retrospectively evaluated the tolerability and efficacy of afatinib in 10 patients (the majority elderly) with a low PS score (2 or 3), who had advanced refractory adenocarcinoma and were carrying active epidermal growth factor receptor mutations. Afatinib was administered at a starting dosage of 20 or 30mg/day, followed by 10mg increases in dose up to a maximum dosage of 40mg/day. RESULTS: The median patient age was 76 years and 50% of the patients had a PS of 3. The patients had previously been treated with gefitinib and/or erlotinib, with a median number of three chemotherapy regimens. All the patients received at least 30mg/day of afatinib. Eight patients did not receive the 40mg/day dosage because of patient refusal due to grade 2 diarrhea (n=6) or the judgment of the doctor (n=2). One patient discontinued the treatment because of drug-induced interstitial lung disease. The most frequent adverse event was grade 2 diarrhea. The objective response rate was 11% and the PS score of five cases improved after afatinib therapy. The median progression-free survival and overall survival periods were 3.6 months and 5.8 months, respectively. CONCLUSIONS: A low starting dosage of afatinib might enable elderly or low PS patients with advanced refractory NSCLC to receive this drug as salvage therapy.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Terapia Recuperativa , Afatinib , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Diarrea/inducido químicamente , Esquema de Medicación , Receptores ErbB/genética , Femenino , Humanos , Grasa Intraabdominal , Enfermedades Pulmonares Intersticiales/inducido químicamente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Mutación , Quinazolinas/efectos adversos , Fármacos Sensibilizantes a Radiaciones/efectos adversos , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1*27) is known to impair the effect of UGT in basic research; however, little clinical investigation has been conducted. To evaluate the effect of the UGT1A1*27 polymorphism in irinotecan therapy, we conducted a prospective study. METHODS: Eligibility criteria included: lung cancer patients; scheduled irinotecan therapy doses of single ≥ 80, combination ≥ 50, radiation with single ≥ 50, or radiation with combination ≥ 40 mg/m(2); age ≥ 20; and Eastern Cooperative Oncology Group performance score (PS) 0-2. Patients were examined for UGT1A1*28 and *6 polymorphisms and received irinotecan. When the UGT1A1*28 polymorphism was detected, a search for UGT1A1*27 was conducted. Fifty patients were enrolled, with 48 patients determined eligible. RESULTS: UGT1A1 polymorphisms *28/*28, *6/*6, *28/*6, *28/-, *6/-, -/- observed 0 (0%), 1 (2%), 1 (2%), 7 (15%), 17 (35%) and 22 (46%), respectively. UGT1A1*27 were examined in nine patients including one ineligible patient; however, no polymorphisms were found. The study ceased after interim analysis. In an evaluation of the side effects of irinotecan, patients with UGT1A1*28 and UGT1A1*6 polymorphisms had a higher tendency to experience febrile neutropenia than wild type (25% and 32% vs. 14%). Incidences of grade 3/4 leukopenia and neutropenia were significantly higher in patients with UGT1A1*28 polymorphisms compared with wild type (75% vs. 32%, P = 0.049; 75% vs. 36%, P = 0.039, respectively). CONCLUSION: Our prospective study did not locate the UGT1A1*27 polymorphism, suggesting that UGT1A1*27 does not significantly predict severe irinotecan toxicity in cancer patients.
RESUMEN
OBJECTIVES: We performed an open-label, multicenter, single-arm phase II study (UMIN ID 000010532) to prospectively evaluate the efficacy and safety of nab-paclitaxel for previously treated patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients with advanced NSCLC who experienced failure of prior platinum-doublet chemotherapy received weekly nab-paclitaxel (100mg/m(2)) on days 1, 8, and 15 of a 21-day cycle until disease progression or the development of unacceptable toxicity. The primary end point of the study was objective response rate (ORR). RESULTS: Forty-one patients were enrolled between September 2013 and April 2015. The ORR was 31.7% (90% confidence interval, 19.3%-44.1%), which met the primary objective of the study. Median progression-free survival was 4.9 months (95% confidence interval, 2.4-7.4 months) and median overall survival was 13.0 (95% confidence interval, 8.0-18.0 months) months. The median number of treatment cycles was four (range, 1-17) over the entire study period, and the median dose intensity was 89.1mg/m(2) per week. Hematologic toxicities of grade 3 or 4 included neutropenia (19.5%) and leukopenia (17.1%), with no cases of febrile neutropenia being observed. Individual nonhematologic toxicities of grade 3 or higher occurred with a frequency of <5%. CONCLUSION: Weekly nab-paclitaxel was associated with acceptable toxicity and a favorable ORR in previously treated patients with advanced NSCLC. Our results justify the undertaking of a phase III trial comparing nab-paclitaxel with docetaxel in this patient population.
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Albúminas/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Paclitaxel/administración & dosificación , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Esquema de Medicación , Femenino , Genes erbB-1 , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Retratamiento , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the efficacy and toxicity of a novel combination treatment using concurrent radiotherapy with cisplatin plus UFT, which is comprised of uracil and tegafur, in locally advanced non-small cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: In this Phase II trial, patients with unresectable stage III NSCLC were treated with the oral administration of UFT (400 mg/m(2)/d tegafur) on days 1-14 and days 29-42 whereas 80 mg/m(2) cisplatin was administered i.v. on days 8 and 36. Radiotherapy, with a total dose of 60 Gy, was delivered in 30 fractions from day 1. RESULTS: Seventy patients were enrolled and eligible, as follows: 57 males/13 females; mean age 61 ranging from 36 to 74; performance status 0/1:45/25; stage IIIA/IIIB, 14/56. A complete response was observed in two patients and a partial response in 54 patients, and the overall response rate was 81% (95% confidence interval; 70-89%). The median survival, the 1- and 2-year survival rates were 16.5 months, 67% and 33%, respectively. Grade 3/4 leukopenia occurred in 14%/1% of the patients. Grades 3 non-hematological toxicities were only reported in three patients with nausea, two with esophagitis and one with pneumonitis whereas no grade 4 non-hematological toxicity was observed. CONCLUSIONS: UFT plus cisplatin with concurrent radiotherapy is considered to be a feasible and effective treatment for locally advanced NSCLC patients. Additional study of this concurrent chemoradiotherapy is warranted.
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Antimetabolitos Antineoplásicos/farmacología , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Cisplatino/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Radioterapia , Tegafur/farmacología , Uracilo/farmacología , Adulto , Anciano , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: It is not clear whether there is a difference in benefit of chemotherapy between small cell lung cancer (SCLC) patients with pre-existing idiopathic interstitial pneumonias (IIPs) and non-small cell lung cancer (NSCLC) patients with IIPs. PATIENTS AND METHODS: We performed a retrospective study of the overall survival (OS) between advanced lung cancer patients with IIPs (n=28) and those without IIPs (n=145). RESULTS: The OS in NSCLC patients with IIPs was shorter than in those without IIPs (median OS, 10.6 vs. 27.9 months, p=0.008) but the OS in SCLC patients with IIPs was not inferior to that of those without IIPs (12.7 vs. 14.8 months, p=0.835). Multivariate analysis showed that the small number of regimens increased the risk of mortality, instead of pre-existing IIPs. CONCLUSION: The continuation of chemotherapy in SCLC patients with IIPs made it possible to have a similar prognosis to that in those without IIPs.