Erlotinib as single agent first line treatment in locally advanced or metastatic activating EGFR mutation-positive lung adenocarcinoma (CEETAC): an open-label, non-randomized, multicenter, phase IV clinical trial.

BACKGROUND: Erlotinib is approved for the first line treatment of epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. Since the number of prospective studies in Caucasian patients treated in routine clinical setting is limited we conducted a multicenter, phase IV clinical trial to determine the efficacy and safety of erlotinib and to demonstrate the feasibility of the validated standardized companion diagnostic method of EGFR mutation detection. METHODS: 651 chemonaive, cytologically or histologically verified advanced stage lung adenocarcinoma patients from Hungary, Turkey and Latvia were screened for exon19 microdeletions and exon21 L858R EGFR mutations using the companion diagnostic EGFR test. EGFR mutation-positive, locally advanced or metastatic lung adenocarcinoma patients received as first line treatment erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS). RESULTS: 62 EGFR mutation-positive patients (9.5% of screened) were included in the safety/intent-to-treat cohort. Median PFS was 12.8 months (95%CI, 9.9-15.8), objective response rate and one-year survival was 66.1% and 82.5%, respectively. Most frequent treatment related adverse events were diarrhoea and rash. Eastern Oncology Cooperative Group Performance Status (ECOG PS), smoking status and M1a/M1b disease stage were significant prognosticators of PFS (p = 0.017, p = 0.045 and p = 0.002, respectively). There was no significant difference in PFS between the subgroups stratified by gender, age or exon19 vs exon21 mutation. CONCLUSIONS: Our study confirmed the efficacy and safety of first line erlotinib monotherapy in Caucasian patients with locally advanced or metastatic lung adenocarcinoma carrying activating EGFR mutations based on the screening with the approved companion diagnostic procedure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01609543.

Comprehensive out-patient pulmonary rehabilitation: Treatment outcomes in early and late stages of chronic obstructive pulmonary disease.

BACKGROUND: The aim was to evaluate the outcomes of a comprehensive pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) and to establish whether in early disease stage PR is as effective as in late stages of disease. METHODS: A total of 55 stable COPD patients, 28 with early and 27 with late disease stages, were assessed. Patients underwent a comprehensive out-patient PR program for 8 weeks. To eluciate the effects of PR and compare the level of improvement; lung function, dyspnea sensation [Medical Research Council (MRC)], body composition [body mass index (BMI), fat free mass (FFM), fat free mass index (FFMI)], exercise capacity [incremental shuttle walking test, endurance shuttle walking test], health related quality of life (HRQoL) with St. George Respiratory Disease Questionnaire, psycohological status (Hospital anxiety-depression (HAD) scale) were evaluated before and after PR. RESULTS: At the end of PR in the early disease stage group, the improvement in forced vital capacity (FVC) reached a statistically significant level (P < 0.05). In both disease stages, there were no significant differences in BMI, FFM, and FFMI. The decrease in exertional dyspnea for the two groups evaluated with the modified BORG scale were not found statistically significant, though the dyspnea scores evaluated with MRC showed significant improvements (P < 0.001). HRQoL and exercise capacity were significantly improved for the two groups (P < 0.001). Psychological status evaluated with the HAD scale improved after PR (P < 0.001) both in early and late stages. Gainings in the study parameters did not differ in the early and the late disease stages. CONCLUSIONS: These results showed that patients with COPD had benefited from a comprehensive PR program in an out-patient setting regardless of disease severity. Even patients with earlier stage of disease should be referred and encouraged to participate in a PR program.

Vascular events in lung cancer.

BACKGROUND AND AIMS: In lung cancer, many factors have prognostic significance, including thrombocytosis, which is frequently observed. Associations between vascular events, which are the outcomes of paraneoplastic symptoms, and mortality and morbidity has been evaluated in many studies. The aim of the present study was to evaluate the relationship between thrombocytosis and vascular events. MATERIALS AND METHODS: In total, 281 patients, who were histopathologically diagnosed with lung cancer between March 2007 and August 2009, were evaluated retrospectively. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) software (ver. 11.5 for Windows). Analysis of the distribution of constant variance for normality was assessed using the Shapiro-Wilk test. Nominal variables were evaluated using Pearson's chi-squared or Fisher's exact chi-squared tests. Significant correlations between continuous variables were investigated using Spearman's correlation test. RESULTS: Of the 281 patients, 234 (83.3%) were males and 47 (16.7%) were females, with a median age of 60.6 (31-83 years). Histopathologically, 40 (14.2%) were diagnosed with small-cell lung cancer and 241 (85.8%) with non-small cell lung cancer. In total, 17 (6.04%) vascular events were identified: 11 (64.7%) deep vein thromboses, three (17.6%) pulmonary thromboembolisms, one (5.9%) cerebral arterial thrombosis, and one (5.9%) vena cava superior thrombosis. Thrombocytosis was not determined during thrombosis, but during subsequent visits. CONCLUSIONS: Thrombocytosis is frequently observed in patients with lung cancer. Further prospective studies are required to evaluate the need for prophylactic anticoagulants in these patients. The association between vascular events and survival, the next step of the present study, will be evaluated prospectively.

Nutritional status of COPD patients with acute exacerbation.

The prevalence and features of nutritional status in patients with chronic obstructive pulmonary disease (COPD) have been studied extensively in stable conditions, but are poorly defined in the presence of an acute exacerbation. The aim of this study is to evaluate the nutritional status of COPD patients with acute exacerbation and possible relationship between nutritional parameters and pulmonary functions. The study group consisted of 53 COPD patients acutely admitted to the hospital for standardized medical treatment. The nutritional status of patients was assessed by anthropometric measurements, biochemical analysis, and immunologic testing. The patients were divided into two groups as having severe (FEV1 < 50%) and mild to moderate (FEV1 ? 50%) COPD and weight loss greater than 5% for the comparison of the study parameters. Ideal body weight (IBW%) was found as 104.42 +/- 4.30 in severe COPD, where as it was 115.31 +/- 7.28 in mild to moderate COPD group (p= 0.07). There was no relationship demonstrated between IBW% and FEV1. IBW% was correlated with DLCO for the total study population (r= 0.353, p= 0.035). Weight loss greater than 5% of body weight (BW) was observed in 54% of patients. Comparison of the patient's actual weight to their usual weight revealed statistically significant weight loss (p< 0.01). Mean values of serum albumin, transferrin were found in normal range. Delayed type hypersensitivity skin test revealed normal immune status. When the study parameters were compared, no any statistically significant differences in parameters related to nutritional status were detected, between severe and mild to moderate COPD groups. As a statistically significant weight loss was found between the actual and usual weights of the patients, monitoring of nutritional parameters and eventual dietetic treatment should also be included in the goals of the medical treatment of patients with COPD in acute exacerbation.

Short-term effect of nasal intermittent positive-pressure ventilation in patients with restrictive thoracic disease.

BACKGROUND: The use of nasal intermittent positive pressure ventilation (NIPPV) would be expected to ameliorate dyspnea, ventilatory capacity and exercise tolerance durability in individuals with hypercapnic respiratory failure secondary to restrictive thoracic disease. OBJECTIVES: The purpose of this study was to determine the short-term effect of NIPPV on respiratory muscle endurance, exercise capacity and respiratory functions in patients with chronic respiratory failure due to restrictive thoracic disease. METHODS: Twelve patients with chronic ventilatory failure due to restrictive thoracic disease underwent nasal bilevel positive airway pressure (BiPAP) ventilation for 2 h a day during 15 consecutive days. The effects were assessed by spirometry, arterial blood gas analysis, 6-min walking test, sensation of dyspnea according to the American Thoracic Society dyspnea scoring scales (ATS) and surface electromyogram of the diaphragm (EMGdi) before and after the study (on day 15). RESULTS: Nasal BiPAP reduced the ATS dyspnea score from 2.5 +/- 0.9 to 1.6 +/- 0.4 (p < 0.01). Distances walked in 6 min increased from 320.66 +/- 93.56 to 382.41 +/- 121.20 m (p < 0.05). Comparison of baseline with levels after nasal BiPAP ventilation showed a statistically significant improvement in PaCO(2) (p < 0.05). Forced vital capacity increased from 35 to 50% of the predicted value (p < 0.01). There were no statistically significant reductions in the amplitude of EMGdi after the therapy. CONCLUSION: These results indicate that NIPPV delivered via nasal BiPAP improves respiratory functions, exercise capacity, and reduces dyspnea in the short term in patients with chronic respiratory failure due to restrictive thoracic disease. Whether such short-term improvements can be sustained merits further study.