A phase II trial of erlotinib in patients with EGFR wild-type advanced non-small-cell lung cancer.

PURPOSE: There is as yet no optimal treatment regimen for patients with epidermal growth factor receptor (EGFR) gene wild-type non-small-cell lung cancer (NSCLC) that has progressed despite cytotoxic chemotherapy. This trial was performed to evaluate the efficacy and toxicity of erlotinib, a tyrosine kinase inhibitor of EGFR, in Japanese patients with EGFR wild-type tumors. METHODS: Patients with stage III/IV or postoperative recurrence of NSCLC whose tumors have wild-type EGFR were eligible. Erlotinib (150 mg/day) was administered until disease progression or unacceptable toxicity occurred. The primary end point was disease control rate (DCR). RESULTS: Thirty-one patients (23 men and 8 women; median age, 71 years; range, 31-89) were enrolled between January 2008 and June 2011. Twenty-one had adenocarcinoma, nine had squamous cell carcinoma, and one had large cell carcinoma. Ten, nine, eight, and four patients showed performance status 0, 1, 2, and 3, respectively. Erlotinib was administered following the median 3.1 regimens of cytotoxic chemotherapies. One patient achieved complete response, four showed partial response, and eight had stable disease. Thus, response rate was 17.2%, and DCR was 44.8%. Skin rash was the most common side effect (80.6%). Two patients developed interstitial lung disease. Nevertheless, all of these events were reversible, and there were no treatment-related deaths. The median progression-free survival and survival times were 2.1 and 7.7 months, respectively. CONCLUSION: Erlotinib might be an alternative option for patients resistant to cytotoxic chemotherapy even in those with EGFR wild-type NSCLC.

Efficacy of continuous positive airway pressure on arrhythmias in obstructive sleep apnea patients.

The purpose of this study was to determine the relationship between obstructive sleep apnea (OSA) and cardiovascular disorders in a large Japanese population, and to assess the efficacy of continuous positive airway pressure (CPAP) in the treatment of OSA-associated arrhythmias. The study population comprised 1394 Japanese subjects (1086 men and 308 women) who were divided into four groups on the basis of polysomnography (PSG) analysis as follows: the no sleep apnea (N-SA) group (n = 44, apnea-hypopnea index [AHI] < 5), the mild OSA (Mi-OSA) group (n = 197, 5 < AHI < 15), the moderate OSA (Mo) group (n = 368, 15 < AHI < 30), and severe OSA (SOSA) group (n = 785, AHI < 30). The following baseline characteristics were significantly associated with OSA: age (P < 0.001), gender (P < 0.001), body mass index (P < 0.001), hypertension (P < 0.001), diabetes (P = 0.009), and hyperlipidemia (P = 0.013). In the OSA group, PSG revealed the predominance of paroxysmal atrial fibrillation (PAF) (P = 0.051), premature atrial complex short run (P < 0.005), premature ventricular complex (PVC, P = 0.004), sinus bradycardia (P = 0.036), and sinus pause (arrest >2 s, P < 0.001) during the PSG recording. A total of 316 patients from the group underwent CPAP titration and were then re-evaluated. Continuous positive airway pressure therapy significantly reduced the occurrences of PAF (P < 0.001), PVC (P = 0.016), sinus bradycardia (P = 0.001), and sinus pause (P = 0.004). The results of this study demonstrate a significant relationship between OSA and several cardiac disorders, and also demonstrate the efficacy of CPAP in preventing OSA-associated arrhythmias in a large population of Japanese patients.

Valve repair improves central sleep apnea in heart failure patients with valvular heart diseases.

BACKGROUND: Recent studies suggest that treatment of heart failure (HF) could improve cardiac function and sleep apnea syndrome (SAS), but it is unknown how cardiac surgery may affect SAS in HF patients. Relationships between HF with valvular heart diseases and 2 types of SAS (obstructive sleep apnea (OSA) and central sleep apnea (CSA)) were examined. The effects of valve repair surgery on OSA and CSA was also investigated. METHODS AND RESULTS: Polysomnography, echocardiography and right cardiac catheterization were used to study 150 severe HF patients with mitral valvular and/or aortic valvular diseases. Significant associations between SAS and age, gender, body mass index, or hypertension were observed. The value of the CSA-apnea index (AI) was significantly correlated with pulmonary capillary wedge pressure (PCWP) and mean pulmonary artery pressure (PAP). These associations were not identified for OSA-AI. Valve repair surgery was used to treat 74 patients with severe SAS. The treatment led to a significant improvement in PCWP and mean PAP, and CSA-AI, but not in OSA-AI. CONCLUSIONS: These findings suggest close associations between CSA and cardiac function in HF patients with valvular heart diseases. Furthermore, improvement of cardiac function with valvular surgery reduces the severity of CSA in HF patients with valvular heart diseases.

Characteristics of Japanese patients with complex sleep apnea syndrome: a retrospective comparison with obstructive sleep apnea syndrome.

OBJECTIVE: The prevalence of complex sleep apnea syndrome (CompSAS) among Asian patients with obstructive sleep apnea syndrome (OSAS) has not yet been reported. Distinguishing CompSAS from pure OSAS is difficult using only diagnostic polysomnography (PSG). We examined the prevalence of CompSAS in Japanese patients with OSAS and the possibility to distinguish CompSAS from pure OSAS by analyzing the severity of respiratory events based on either sleep body position or sleep stage using a diagnostic PSG. PATIENTS AND METHODS: A retrospective chart review of 297 consecutive Japanese patients who were 15 years of age or older with a primary diagnosis of OSAS who were referred for CPAP titration (AHI> or =20 events/hr). RESULTS: Seventeen patients (5.7%) out of the 297 patients who had an obstructive apnea hypopnea index (AHI) of 20 or higher showed adverse increases in central apnea index (CAI) by the treatment with CPAP whereas obstructive apnea index (OAI) and mixed apnea index (MAI) were significantly decreased. In the results, the AHI on the PSG for CPAP titration reached only approximately half of the values on the diagnostic PSG. In these CompSAS patients, both the total CAI and the CAI in the supine position during NREM sleep on the diagnostic PSG were significantly higher than those in the OSAS group. The sleep body position did not so strongly affect the AHI, OAI and MAI in the CompSAS group. Multiple, stepwise, and logistic regression analyses revealed that the CAI in the supine position during NREM (p=0.026) was a significant variable to distinguish CompSAS from OSAS statistically although the variables were within the normal range. CONCLUSION: The prevalence of CompSAS in Japanese OSAS patients may be lower when compared with Caucasian patients. The increase of CAI in the supine position during NREM sleep on diagnostic PSG may be a characteristic feature in CompSAS.