Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer

BACKGROUND: Gefitinib, an oral agent of epidermal growth factor receptor tyrosine kinase inhibitor, has a certain efficacy against non-small cell lung cancer (NSCLC). Several predictive factors of gefitinib sensitivity have been well described. However, few studies have investigated the clinical features of gefitinib-responders. In the present study, we analyzed the response and disease progression of primary and metastatic lesions to gefitinib in responders and the results of gefitinib readministration following temporary cessation of gefitinib upon progression of initial gefitinib treatment and other treatments. METHOD: We retrospectively evaluated the clinical courses of 27 NSCLC patients who received gefitinib and achieved either a complete or partial response. RESULTS: The best-response rate and disease-control rate against the initial chemotherapy for the gefitinib-responders were 27.3% and 77.3%, respectively. Favorable efficacy was observed in the primary lesion and metastases to the lung, liver and brain, while there was no obvious effect on bone metastasis. The primary lesion and intrapulmonary metastasis were the sites of major recurrence. Median progression-free survival was 13.8 months, median duration of gefitinib treatment was 17.0 months and median overall survival was 29.2 months. Some of the patients who experienced disease progression after responding to gefitinib were again sensitive to readministration of gefitinib following temporary cessation of gefitinib and other treatments. CONCLUSION: Patients may still be expected to have prolonged survival if they once responded to gefitinib and then underwent various subsequent treatments followed by readministration of gefitinib. These findings might provide valuable information for the management of gefitinib-responders

Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer

BACKGROUND: Gefitinib, an oral agent of epidermal growth factor receptor tyrosine kinase inhibitor, has a certain efficacy against non-small cell lung cancer (NSCLC). Several predictive factors of gefitinib sensitivity have been well described. However, few studies have investigated the clinical features of gefitinib-responders. In the present study, we analyzed the response and disease progression of primary and metastatic lesions to gefitinib in responders and the results of gefitinib readministration following temporary cessation of gefitinib upon progression of initial gefitinib treatment and other treatments. METHOD: We retrospectively evaluated the clinical courses of 27 NSCLC patients who received gefitinib and achieved either a complete or partial response. RESULTS: The best-response rate and disease-control rate against the initial chemotherapy for the gefitinib-responders were 27.3% and 77.3%, respectively. Favorable efficacy was observed in the primary lesion and metastases to the lung, liver and brain, while there was no obvious effect on bone metastasis. The primary lesion and intrapulmonary metastasis were the sites of major recurrence. Median progression-free survival was 13.8 months, median duration of gefitinib treatment was 17.0 months and median overall survival was 29.2 months. Some of the patients who experienced disease progression after responding to gefitinib were again sensitive to readministration of gefitinib following temporary cessation of gefitinib and other treatments. CONCLUSION: Patients may still be expected to have prolonged survival if they once responded to gefitinib and then underwent various subsequent treatments followed by readministration of gefitinib. These findings might provide valuable information for the management of gefitinib-responders

Airway Remodeling and Airway Smooth Muscle in Asthma

Airway remodeling in asthma has been recognized as structural changes of airways such as smooth muscle hypertrophy (an increase in size of airway smooth muscle cells) and hyperplasia (an increase in the number of airway smooth muscle cells), thickening and fibrosis of sub-epithelial basement membrane, hypertrophy of bronchial glands, goblet cell hyperplasia, and thickening of airway epithelium. In these pathological changes, airway smooth muscle remodeling has been recognized as one of the most important factors related to in vitro and in vitro airway responsiveness and the severity of asthma. Both hypertrophy and hyperplasia have been shown in asthmatic airways by morphometrical analyses, although there is a wide variation in the contribution of each mechanism in each patient. Such changes could also be recognized as a phenotypic modulation of airway smooth muscle. On the background of airway smooth muscle remodeling, the existence of several contributing factors, such as inflammatory mediators, growth factors, cytokines, extra-cellular matrix proteins, and genetic factors have been suggested. On the other hand, recent studies revealed that airway smooth muscle could also be a source of inflammatory mediators promoting airway inflammation. In this article, the recent understanding in the mechanisms of airway smooth muscle remodeling in asthma, its relations to airway inflammation and airway physiology, and possible usefulness of early intervention with inhaled glucocorticoids have been discussed

Exhaled Nitric Oxide (FeNO) as a Non-Invasive Marker of Airway Inflammation

Nitric oxide (NO), previously very famous for being an environmental pollutant in the field of pulmonary medicine, is now known as the smallest, lightest, and most famed molecule to act as a biological messenger. Furthermore, recent basic researches have revealed the production mechanisms and physiological functions of nitric oxide in the lung, and clinical researches have been clarifying its tight relation to airway inflammation in asthma. On the bases of this knowledge, fractional nitric oxide (FeNO) has now been introduced as one of the most practical tools for the diagnosis and management of bronchial asthma

Virtual bronchoscopic navigation combined with endobronchial ultrasound to diagnose small peripheral pulmonary lesions : a randomised trial

Background: Bronchoscopy using endobronchial ultrasound (EBUS) can help to diagnose small peripheral pulmonary lesions. However, although biopsy sites can be confirmed, a bronchoscope cannot be guided in EBUS. Virtual bronchoscopic navigation (VBN) can guide a bronchoscope with virtual images, but its value has not been confirmed. Methods: This prospective multicentre study examines the value of VBN-assisted EBUS for diagnosing small peripheral pulmonary lesions. 199 patients with small peripheral pulmonary lesions (diameter ≤ 30 mm) were randomly assigned to VBN-assisted (VBNA) or non-VBN-assisted (NVBNA) groups. A bronchoscope was introduced into the target bronchus of the VBNA group using the VBN system. Sites of specimen sampling were verified using EBUS with a guide sheath under fluoroscopy. Results: The diagnostic yield was higher for the VBNA than for the NVBNA group (80.4% vs 67.0%; p=0.032). The duration of the examination and time elapsed until the start of sample collection were reduced in the VBNA compared with the NVBNA group (median (range), 24.0 (8.7-47.0) vs 26.2 (11.6-58.6) min, p=0.016) and 8.1 (2.8-39.2) vs 9.8 (2.3-42.3) min, p=0.045, respectively). The only adverse event was mild pneumothorax in a patient from the NVBNA group. Conclusions: The diagnostic yield for small peripheral pulmonary lesions is increased when VBN is combined with EBUS

Successful Treatment of Infection-Triggered Acute Exacerbation of Idiopathic Pulmonary Fibrosis with Corticosteroids Combined with Macrolides

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia (IP) with poor prognosis. Acute exacerbation (AE) of IPF (AE-IPF) has a substantial and sometimes fatal impact on prognosis. An effective pharmaceutical treatment for AE-IPF is lacking. Macrolides (MACs) have an anti-bacterial activity and anti-inflammatory effects, and IPF treatment with these agents has been recently reported. This report describes a case of infection-triggered AE-IPF treated with corticosteroids (CSs) combined with MACs. A 61-year-old male patient suffering from IPF previously treated with methyl-prednisolone (mPSL) (8 mg/day) was admitted because of fever, dry cough, and dyspnea. Reticular opacities (RO) on chest roentgenogram and ground-glass opacities (GGO) on high-resolution computed tomography (HRCT) exacerbated. The patient was diagnosed with influenza A and influenza A-triggered AE-IPF and was treated with peramivir and mPSL (1 g/day) for 3 days. RO on chest roentgenogram further exacerbated, prompting the addition of erythromycin (EM), in consideration of its anti-inflammatory effects. Thereafter, the patient was successfully treated with mPSL or PSL combined with EM. During the clinical course, he experienced cytomegalovirus (CMV)-induced IP and/or CMV-triggered AE-IPF, being successfully treated with ganciclovir and mPSL or PSL combined with EM. Thereafter, the patient was treated with CSs combined with EM or clarithromycin. Approximately 3 months after initiating EM, RO on chest roentgenogram and GGO on HRCT considerably improved. This case shows that treatment with CSs combined with MACs may be effective in some cases of infection-triggered AE-IPF