RESUMO
BACKGROUND: Quavonlimab (MK-1308), a novel anti-CTLA-4 antibody, in combination with pembrolizumab was investigated in a phase I study. PATIENTS AND METHODS: Dose-escalation (DE) phase: patients with advanced/metastatic solid tumors received an initial flat dose of quavonlimab as monotherapy [25 mg (cohort 1), 75 mg (cohort 2), or 200 mg (cohort 3)] followed by four treatments of the same quavonlimab dose plus pembrolizumab every 3 weeks (Q3W). Dose-confirmation phase (DC): patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) received first-line quavonlimab [25 mg Q3W (arm A), 25 mg Q6W (arm B), 75 mg Q6W (arm C), or 75 mg Q3W (arm E)] plus pembrolizumab. Primary objectives were safety and tolerability and establishment of the recommended phase II dose (RP2D) of quavonlimab when used with pembrolizumab. Objective response rate (ORR) was a secondary endpoint. Efficacy based on PD-L1 expression, tumor mutational burden (TMB), and changes in circulating CD4+/CD8+ cells were exploratory endpoints. RESULTS: Thirty-nine patients were enrolled in DE [n = 14 (cohort 1); n = 17 (cohort 2); n = 8 (cohort 3)] and 134 in DC [n = 40 (arm A); n = 40 (arm B); n = 40 (arm C); n = 14 (arm E)]. Maximum-tolerated dose was not reached. Grade 3-5 treatment-related adverse events (AEs; graded according to NCI CTCAE v4.03) occurred in 0%, 23.5%, and 75.0% of patients in DE cohorts 1, 2, and 3, respectively, and 35.0%, 30.0%, 35.0%, and 57.1% of patients in DC arms A, B, C, and E, respectively. Efficacy was observed at all dose levels/schedules in patients with NSCLC. ORRs were 40.0% [95% confidence interval (CI), 24.9-56.7; arm A], 37.5% (95% CI, 22.7-54.2; arm B), 27.5% (95% CI, 14.6-43.9; arm C), and 35.7% (95% CI, 12.8-64.9; arm E). PD-L1 expression and total number of circulating CD4+ cells correlated with ORR. CONCLUSIONS: Quavonlimab 25 mg Q6W plus pembrolizumab demonstrated similar efficacy and a better safety profile among all quavonlimab doses/schedules evaluated; this regimen was the chosen RP2D.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
BACKGROUND: Primary analysis of the phase III study WJTOG 3405 demonstrated superiority of progression-free survival (PFS) for gefitinib (G) in patients treated with the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) gefitinib compared with cisplatin plus docetaxel (CD) as the first-line treatment of stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. This report presents final overall survival (OS) data. PATIENTS AND METHODS: Patients were randomized between G (250 mg/day orally) and cisplatin (80 mg/m2 intravenously) plus docetaxel (60 mg/m2 i.v.), administered every 21 days for three to six cycles. After the exclusion of 5 patients, 172 patients (86 in each group, modified intention-to-treat population) were included in the survival analysis. OS was re-evaluated using updated data (data cutoff, 30 September 2013; median follow-up time 59.1 months). The Kaplan-Meier method and the log-rank test were used for analysis, and hazard ratios (HRs) for death were calculated using the Cox proportional hazards model. RESULTS: OS events in the G group and CD group were 68 (79.1%) out of 86 and 59 (68.6%) out of 86, respectively. Median survival time for G and CD were 34.9 and 37.3 months, respectively, with an HR of 1.252 [95% confidence interval (CI): 0.883-1.775, P = 0.2070]. Multivariate analysis identified postoperative recurrence and stage IIIB/IV disease as independent prognostic factors, with an HR of 0.459 (95% CI: 0.312-0.673, P < 0.001). Median survival time (postoperative recurrence versus stage IIIB/IV disease) were 44.5 and 27.5 months in the G group and 45.5 and 32.8 months in the CD group, respectively. CONCLUSION: G did not show OS benefits over CD as the first-line treatment. OS of patients with postoperative recurrence was better than that of stage IIIB/IV disease, even though both groups had metastatic disease.This study was registered with UMIN (University Hospital Medical Information Network in Japan), number 000000539.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Gefitinibe/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Docetaxel/efeitos adversos , Receptores ErbB/genética , Feminino , Gefitinibe/efeitos adversos , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Eribulin is a microtubule dynamics inhibitor with a novel mechanism of action. This phase 3 study aimed to compare overall survival (OS) in patients with heavily pretreated non-small cell lung cancer (NSCLC) receiving eribulin to treatment of physician's choice (TPC). PATIENTS AND METHODS: Patients with advanced NSCLC who had received ≥2 prior therapies, including platinum-based doublet and epidermal growth factor receptor tyrosine kinase inhibitor, were randomly assigned to receive eribulin or TPC (gemcitabine, pemetrexed, vinorelbine, docetaxel). The primary endpoint was OS. Secondary endpoints were progression-free survival and objective response rate. RESULTS: Five hundred and forty patients were randomized to either eribulin (n = 270) or TPC (n = 270). Median OS for eribulin and TPC was the same: 9.5 months [hazard ratio (HR): 1.16; 95% confidence interval: 0.95-1.41; P = 0.13]. Progression-free survival for eribulin and TPC was 3.0 and 2.8 months, respectively (HR: 1.09; 95% confidence interval: 0.90-1.32; P = 0.39). The objective response rate was 12% for eribulin and 15% for TPC. Clinical benefit rate (eribulin, 57%; TPC, 55%) and disease control rate (eribulin, 63%; TPC, 58%) were similar between treatment arms. The most common adverse event was neutropenia, which occurred in 57% of eribulin patients and 49% of TPC patients at all grades. Other non-hematologic side-effects were manageable and similar in both groups except for peripheral sensory neuropathy (all grades; eribulin, 16%; TPC, 9%). CONCLUSION: This phase 3 study did not demonstrate superiority of eribulin over TPC with regard to overall survival. However, eribulin does show activity in the third-line setting for NSCLC. TRIAL REGISTRATION ID: www.ClinicalTrials.gov; NCT01454934.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Furanos/uso terapêutico , Cetonas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Furanos/efeitos adversos , Humanos , Cetonas/efeitos adversos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise de SobrevidaRESUMO
BACKGROUND: A previous clinical study in non-small cell lung cancer (NSCLC) patients in Western countries suggested the potential for combination of a first-in-class non-ATP-competitive c-Met inhibitor tivantinib with an epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib. Polymorphisms of CYP2C19, the key metabolic enzyme for tivantinib, should be addressed to translate the previous Western study to Asian population, because higher incidence of poor metabolisers (PMs) is reported in Asian population. METHODS: Japanese patients with advanced/metastatic NSCLC received tivantinib in combination with erlotinib to evaluate safety and pharmacokinetics. Doses of tivantinib were escalated separately for extensive metabolisers (EMs) and PMs. RESULTS: Tivantinib, when combined with erlotinib, was well tolerated up to 360 mg BID for EMs and 240 mg BID for PMs, respectively. Among 25 patients (16 EMs and 9 PMs), the adverse events (AEs) related to tivantinib and/or erlotinib (>20%, any grade) were rash, diarrhoea, dry skin and nausea. Grade ≥3 AEs were leukopenia, anaemia and neutropenia. No dose-limiting toxicity was observed. Pharmacokinetics profile of tivantinib was not clearly different between the combination and monotherapy. Three partial response and three long-term stable disease (≥24 weeks) were reported. CONCLUSION: Two doses of tivantinib in combination with erlotinib were recommended based on CYP2C19 genotype: 360 mg BID for EMs and 240 mg BID for PMs.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hidrocarboneto de Aril Hidroxilases/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirrolidinonas/administração & dosagem , Quinazolinas/administração & dosagem , Quinolinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Povo Asiático , Carcinoma Pulmonar de Células não Pequenas/etnologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Citocromo P-450 CYP2C19 , Progressão da Doença , Cálculos da Dosagem de Medicamento , Cloridrato de Erlotinib , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Pirrolidinonas/efeitos adversos , Pirrolidinonas/farmacocinética , Quinazolinas/efeitos adversos , Quinazolinas/farmacocinética , Quinolinas/efeitos adversos , Quinolinas/farmacocinéticaRESUMO
BACKGROUND: A phase III study (Lung Cancer Evaluation of TS-1) previously demonstrated noninferiority in terms of overall survival (OS) at interim analysis for carboplatin-S-1 compared with carboplatin-paclitaxel for first-line treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 564 patients were randomly assigned to receive either carboplatin on day 1 plus oral S-1 on days 1-14 or carboplatin-paclitaxel on day 1 every 21 days. Updated results and post hoc subgroup analysis according to tumor histology are presented. RESULTS: The updated analysis revealed a median OS of 15.2 months in the carboplatin-S-1 arm and 13.1 months in the carboplatin-paclitaxel arm, with a hazard ratio (HR) of 0.956 [95% confidence interval (CI) 0.793-1.151], consistent with the previous primary analysis. Median OS was 14.0 months in the carboplatin-S-1 arm and 10.6 months in the carboplatin-paclitaxel arm (HR 0.713; 95% CI 0.476-1.068) for patients with squamous cell carcinoma (SCC), with corresponding values of 15.5 and 13.9 months (HR 1.060; 95% CI 0.859-1.308) for those with non-SCC. CONCLUSIONS: These results establish the efficacy and safety of carboplatin-S-1 in patients with advanced NSCLC regardless of tumor histology.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Paclitaxel/uso terapêutico , Tegafur/uso terapêutico , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Reagentes de Ligações Cruzadas/efeitos adversos , Reagentes de Ligações Cruzadas/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Japão , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/efeitos adversos , Paclitaxel/efeitos adversos , Tegafur/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is predictive for the efficacy of EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer (NSCLC) treatment. We evaluated the performance, sensitivity, and concordance between five EGFR tests. MATERIALS AND METHODS: DNA admixtures (n = 34; 1%-50% mutant plasmid DNA) and samples from NSCLC patients [116 formalin-fixed paraffin-embedded (FFPE) tissue, 29 matched bronchofiberscopic brushing (BB) cytology, and 20 additional pleural effusion (PE) cytology samples] were analyzed. EGFR mutation tests were PCR-Invader, peptide nucleic acid-locked nucleic acid PCR clamp, direct sequencing, Cycleave, and Scorpion Amplification Refractory Mutation System (ARMS). Analysis success, mutation status, and concordance rates were assessed. RESULTS: All tests except direct sequencing detected four mutation types at ≥1% mutant DNA. Analysis success rates were 91.4%-100% (FFPE) and 100% (BB and PE cytology), respectively. Inter-assay concordance rates of successfully analyzed samples were 94.3%-100% (FFPE; kappa coefficients: 0.88-1.00), 93.1%-100% (BB cytology; 0.86-1.00), and 85.0%-100% (PE cytology; 0.70-1.00), and 93.1%-96.6% (0.86-0.93) between BB cytology and matched FFPE. CONCLUSIONS: All EGFR assays carried out comparably in the analysis of FFPE and cytology samples. Cytology-derived DNA is a viable alternative to FFPE samples for analyzing EGFR mutations.
Assuntos
Adenocarcinoma/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Análise Mutacional de DNA/métodos , Receptores ErbB/genética , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Análise de Sequência de DNARESUMO
BACKGROUND: Mature progression-free survival (PFS) data from the phase III J-ALEX study showed superiority for alectinib versus crizotinib [hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.26-0.52; median PFS 34.1 versus 10.2 months, respectively] in advanced ALK (anaplastic lymphoma kinase)-positive non-small-cell lung cancer (NSCLC). Overall survival (OS) data were immature (HR 0.80, 99.8799% CI 0.35-1.82) at the time of data cut-off (30 June 2018). We report final OS data after ≥5 years of follow-up. PATIENTS AND METHODS: ALK inhibitor naive Japanese patients who were chemotherapy naive or had received one prior chemotherapy regimen were enrolled. Patients were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was independent review facility-assessed PFS, with OS (not fully powered) as a secondary endpoint. RESULTS: Median duration of OS follow-up was 68.6 months with alectinib and 68.0 months with crizotinib. Treatment with alectinib did not prolong OS relative to crizotinib (HR 1.03, 95.0405% CI 0.67-1.58; P = 0.9105). Five-year OS rates were 60.9% (95% CI 51.4-70.3) with alectinib and 64.1% (95% CI 54.9-73.4) with crizotinib. In total, 91.3% (n = 95/104) of crizotinib-treated patients and 46.6% (n = 48/103) of alectinib-treated patients received at least one subsequent anticancer therapy. After study drug discontinuation, 78.8% of patients in the crizotinib arm switched to alectinib, while 10.7% of patients in the alectinib arm switched to crizotinib as a first subsequent anticancer therapy. Patients randomized to crizotinib tended to switch treatment earlier than those randomized to alectinib. CONCLUSION: Final OS analysis from J-ALEX did not show superiority of alectinib to crizotinib; this result was most likely confounded by treatment crossover. Alectinib remains a standard of care for the treatment of patients with advanced ALK-positive NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carbazóis , Crizotinibe , Humanos , Japão , Piperidinas , Inibidores de Proteínas Quinases , Análise de SobrevidaRESUMO
BACKGROUND: Atezolizumab (anti-programmed death-ligand 1 [PD-L1]) received approval from the US Food and Drug Administration and European Medicines Agency for previously treated advanced non-small-cell lung cancer based on OAK-a randomised, phase III trial that showed significantly improved survival with atezolizumab versus docetaxel regardless of PD-L1 expression. With longer follow-up, we summarised the characteristics of long-term survivors (LTSs). METHODS: In OAK (NCT02008227), patients were randomised 1:1 to receive atezolizumab or docetaxel until loss of clinical benefit or disease progression, respectively. Overall survival was evaluated after a 26-month minimum follow-up, including in patient subgroups defined by best overall response (BOR). LTSs were defined as patients who lived ≥24 months since randomisation. Non-LTSs died within 24 months, and patients censored before 24 months were excluded from the analysis. The baseline characteristics, including biomarkers, BOR, subsequent non-protocol therapy (NPT) and safety, are reported. RESULTS: Survival benefit with atezolizumab was observed across all patient subgroups defined by BOR. More atezolizumab-treated patients were LTSs versus those treated with docetaxel (28% versus 18%). Most atezolizumab responders were LTSs (77%) versus only 48% of docetaxel responders. However, 21% of atezolizumab-arm LTSs had progressive disease (PD) as BOR, and more atezolizumab-arm LTSs than non-LTSs continued treatment post-PD. Fifty-two percent of docetaxel-arm LTSs received immunotherapy as subsequent NPT. Despite extended treatment duration in atezolizumab-arm LTSs (median, 18 months), atezolizumab was well tolerated. CONCLUSIONS: After >2 years of follow-up, atezolizumab continued to provide durable survival benefit versus docetaxel, with tolerable safety. Atezolizumab-arm LTSs were enriched for patients with high PD-L1 expression and included PD-L1-negative patients. Long-term survival was not limited to responders.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias Pulmonares/mortalidade , Sobreviventes/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Docetaxel/administração & dosagem , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
PURPOSE: To establish dosimetric predictors of radiation esophagitis (RE) in patients treated with a combination of carboplatin, paclitaxel, and radiotherapy. METHODS AND MATERIALS: Three-dimensional radiotherapy plans of 26 patients with non-small-cell lung cancer who received 50-60 Gy of radiotherapy concurrently with weekly administration of carboplatin (AUC 2) and paclitaxel (40-45 mg/m(2)) were reviewed in conjunction with RE. The factors analyzed included the following: percentages of organ volumes receiving >40 Gy (V40), >45 Gy (V45), >50 Gy (V50), and >55 Gy (V55); the length of esophagus (total circumference) treated with >40 Gy (LETT40), >45 Gy (LETT45), >50 Gy (LETT50), and >55 Gy (LETT55); the maximum dose in the esophagus (Dmax); and the mean dose in the esophagus (Dmean). Data were obtained on the basis of superposition algorithm. RESULTS: All factors except Dmax showed statistical correlation with RE. Good correlations were shown between RE and LETT45 (rho = 0.714) and V45 (rho = 0.686). CONCLUSIONS: LETT45 and V45 appear to be useful dosimetric predictors of RE. It is also suggested that Dmax does not predict RE.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Esofagite/etiologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/etiologia , Radioterapia Conformacional , Adulto , Idoso , Área Sob a Curva , Carboplatina/administração & dosagem , Terapia Combinada , Esquema de Medicação , Esofagoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Dosagem RadioterapêuticaRESUMO
We measured exhaled nitric oxide (NO) with a chemiluminescence method to elucidate the clinical significance of the increased concentration of exhaled NO in patients with bronchial asthma. Exhaled NO was measured in 25 patients with bronchial asthma and in 10 healthy control subjects. The concentration of exhaled NO in asthmatics was significantly higher than in the controls (250.4 +/- 30.4,59.9 +/- 9.6 ppb, respectively, p < 0.01). Symptomatic patients (unstable asthmatics) had a higher exhaled NO concentration than did the asymptomatic patients (stable asthmatics) (384.2 +/- 32.5,143.6 +/- 18.8 ppb, respectively, p < 0.01). The exhaled NO concentration was significantly correlated with the peak expiratory flow rate (r = 0.671, p < 0.01) and eosinophil ratio in induced sputum (r = 0.772, p < 0.05), but it was not correlated with the parameters of bronchial hyperactivity (Dmin and PD35 Grs). We conclude that the increased concentration of exhaled NO in patients with bronchial asthma reflects the state of airway inflammation, and we suggest that the measurement of exhaled NO is a useful, non-invasive and simple method for the management of bronchial asthma.
Assuntos
Asma/metabolismo , Óxido Nítrico/metabolismo , Adulto , Asma/patologia , Asma/fisiopatologia , Estudos de Casos e Controles , Eosinófilos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pico do Fluxo Expiratório , Respiração , Escarro/citologiaRESUMO
To elucidate the effect of low molecular weight heparin (LMWH) on the bronchoconstriction, we examined the serial changes of the resistance of respiratory system (Rrs) in ovalbumin (OA)-sensitized guinea pigs after antigen exposure. After sensitization of guinea pigs with repeated OA inhalation, Rrs was measured at immediate asthmatic response (IAR) and late asthmatic response (LAR) with or without LMWH inhalation. Alteration in the number of inflammatory cells of the lung by LMWH inhalation was examined in the broncholaveolar lavage fluid (BALF) and in the histological sections of airway walls. Peak Rrs at 1 min up to 9 min, except 8 min, after antigen exposure significantly decreased by the pretreatment with LMWH inhalation as compared with saline inhalation. Peak Rrs at LAR (after 4 hours up to 24 hours, except 6 hours) also showed a significant decrease in the pretreatment with LMWH inhalation. Pretreatment of LMWH exhibited a decrease of eosinophil percentage in BALF (5.5 +/- 1.2% from 8.2 +/- 0.4% in saline inhalation) and a decrease of infiltrated eosinophil count in airway walls (71.0 +/- 7.3 from 155 +/- 15.8 in saline inhalation). These data show LMWH might play an important role as an inhibitory factor to bronchial asthma.
Assuntos
Asma/fisiopatologia , Broncoconstrição/efeitos dos fármacos , Heparina de Baixo Peso Molecular/farmacologia , Administração por Inalação , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar/citologia , Depressão Química , Cobaias , Heparina de Baixo Peso Molecular/administração & dosagemRESUMO
The combination of docetaxel (TXT), gemcitabine (GEM), and cisplatin (CDDP) produced a regression in a squamous cell carcinoma of the lung that had recurred after radiation therapy plus chemotherapy, and was resistant to the combination of carboplatin (CBDCA) with etoposide (ETP) or paclitaxel (TXL). The patient was a 62-year-old man with squamous cell lung cancer, which was first successfully treated by a combination of radiation therapy and chemotherapy, but showed local recurrence after 8 months. Although the recurrence was treated with CBDCA plus ETP and then TXL, the tumor continued to grow with symptomatic progression of airway stenosis. The tumor began to regress after the regimen of TXT, GEM and CDDP was started. This therapy achieved PR with symptomatic improvement. The combination of TXT, GEM and CDDP may be effective for recurrent non-small-cell lung carcinoma, even in patients that have failed to respond to more than one chemotherapy regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , GencitabinaRESUMO
Psychiatric studies were made on 26 inoperable patients with lung cancer or thymic cancer to exam the possible correlation of chemotherapy and chemotherapy-induced nausea and vomiting. All patients were informed of their disease and how to undergo the therapy. Psychiatric tests of CMI (Cornell Medical, Index), MAS (Manifest Anxiety Scale), SDS (Self-Rating Depression Scale) and QOL questionnaire were performed just before the chemotherapy. SDS and QOL questionnaire were also done after chemotherapy. The patients were given chemotherapy including CDDP (80 mg/m2) and anti-emetic agents of 30 mg of azasetron, 750 mg of methylprednisolone and 1,800 mg of domperidone. The patients showing neurosis, anxiety or depression had significantly high nausea scores, so we concluded that psychiatric support was needed to improve these patients' QOL in chemotherapy.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/psicologia , Náusea/induzido quimicamente , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/psicologia , Vômito/induzido quimicamente , Idoso , Depressão , Feminino , Humanos , Masculino , Escala de Ansiedade Manifesta , Pessoa de Meia-Idade , Inventário de Personalidade , Testes Psicológicos , Qualidade de VidaRESUMO
This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. A total of 221 Japanese patients who received gefitinib (250 mg day(-1)) were examined retrospectively and potential predictive factors analysed. Overall response rate (ORR) was 24.4% and median survival time (MST) was 8.0 months. In a log-rank test, survival was significantly better in females, patients with adenocarcinoma, never-smokers, favourable performance status (PS) and patients with epidermal growth factor receptor (EGFR) mutation. The lower the smoking exposure (Brinkman Index (BI)=cigarettes per day x years smoked), the better the MST (BI 0: 14.5 months, BI <500: 9.5 months, BI 500 to <1000: 6.9 months, BI > or =1000: 4.0 months). Positive-EGFR mutation status and PS 0-1 were independent predictors of favourable prognosis by multivariate analysis. Prognosis was significantly different according to EGFR mutation status (with the same smoking status), but not according to smoking status (with the same EGFR mutation status). EGFR mutation status is the most important independent predictor of survival benefit with gefitinib treatment. Although differences in prognosis were observed according to relative smoking status and smoking exposure, the results suggested that smoking is not a direct predictor of prognosis, yet is a surrogate marker of EGFR mutation status.