Summary Background Several studies have shown the efficacy, tolerability, and ease of administration of pemetrexed—an antifolate antineoplastic agent—in patients with advanced non-small-cell lung ...cancer. We assessed pemetrexed as maintenance therapy in patients with this disease. Methods This randomised double-blind study was undertaken in 83 centres in 20 countries. 663 patients with stage IIIB or IV disease who had not progressed on four cycles of platinum-based chemotherapy were randomly assigned (2:1 ratio) to receive pemetrexed (500 mg/m2 , day 1) plus best supportive care (n=441) or placebo plus best supportive care (n=222) in 21-day cycles until disease progression. Treatment was randomised with the Simon and Pocock minimisation method. Patients and investigators were masked to treatment. All patients received vitamin B12 , folic acid, and dexamethasone. The primary endpoint of progression-free survival and the secondary endpoint of overall survival were analysed by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00102804. Findings All randomly assigned participants were analysed. Pemetrexed significantly improved progression-free survival (4·3 months 95% CI 4·1–4·7 vs 2·6 months 1·7–2·8; hazard ratio HR 0·50, 95% CI 0·42–0·61, p<0·0001) and overall survival (13·4 months 11·9–15·9 vs 10·6 months 8·7–12·0; HR 0·79, 0·65–0·95, p=0·012) compared with placebo. Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group (21 5% vs three 1%). Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo (70 16% vs nine 4%; p<0·0001), specifically fatigue (22 5% vs one 1%, p=0·001) and neutropenia (13 3% vs 0, p=0·006). No pemetrexed-related deaths occurred. Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy (227 51% vs 149 67%; p=0·0001). Interpretation Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer. Funding Eli Lilly.
Waist circumference is a good predictor of the risk of heart diseases, but data on the relationship between waist circumference and pulmonary diseases are sparse. The aim of this study was to ...investigate its influence on pulmonary function regarding exercise capacity in moderate and severe chronic obstructive pulmonary disease (COPD), according to Global Initiative for Lung Diseases (GOLD) stages. During 2009, a total of 70 COPD patients aged 33 to 80 years were stratified into GOLD 2 and GOLD 3 stages. Diagnostic separation between COPD severity groups was made upon percentage of predicted forced expiratory volume in 1 second. Anthropometric measures, lung function testing and prognostic scoring systems were assessed. Logistic regression analysis was used to make comparisons while taking into account the possible confounding factors. Waist circumference did not show substantial variations between GOLD 2 and GOLD 3 stages (p > 0.5). There was a weak positive correlation between waist circumference and percent of predicted 6-minute walking distance (r = 0.237; p = 0.001). Another parameter, suprailiac skinfold, was significantly different between GOLD 2 and GOLD 3 stages (19.41 vs. 15.32 mm; p = 0.047). Although waist circumference is a meaningful marker of abdominal obesity, which influences pulmonary function, we failed to prove its importance in correlation with functional lung capacity in a selected COPD population. However, suprailiac skinfold deserves greater attention and further evaluation.
Summary Background Pemetrexed maintenance therapy significantly improved overall survival and progression-free survival compared with placebo, and had a good safety profile in a phase 3 ...placebo-controlled study in patients with advanced non-small-cell lung cancer (NSCLC). Results for quality of life, symptom palliation, and tolerability are presented here. Methods After four cycles of platinum-based induction therapy, 663 patients with stage IIIB or stage IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (in a 2:1 ratio) from March 15, 2005, to July 20, 2007, using the Pocock and Simon minimisation method to receive pemetrexed (500 mg/m2 every 21 days; n=441) or placebo (n=222) plus best supportive care until disease progression. The primary efficacy data have been reported previously. Patients completed the Lung Cancer Symptom Scale (LCSS) at baseline, after each cycle, and post-discontinuation. Worsening of symptoms was defined as an increase of 15 mm or more from baseline on a 100 mm scale for each LCSS item. The primary outcome for these quality-of-life analyses was time to worsening of symptoms, analysed for all randomised patients. This study is registered with ClinicalTrials.gov , number NCT00102804. Findings Baseline characteristics, including LCSS scores, were well balanced between groups. Baseline LCSS scores were low, indicating low symptom burden for patients without disease progression after completion of first-line treatment. Longer time to worsening was recorded for pain (hazard ratio HR 0·76, 95% CI 0·59–0·99; p=0·041) and haemoptysis (HR 0·58, 95% CI 0·34–0·97; p=0·038) with pemetrexed than with placebo; no other significant differences in analyses of time to worsening were noted. Additional longitudinal analyses showed a greater increase in loss of appetite in the pemetrexed group than in the placebo group (4·3 mm vs 0·2 mm; p=0·028). Rates of resource use were statistically higher for pemetrexed than for placebo: admissions to hospital for drug-related adverse events (19 4% vs none; p=0·001), transfusions (42 10% vs seven 3%; p=0·003), and erythropoiesis-stimulating agents (26 6% vs four 2%; p=0·017). Interpretation Quality of life during maintenance therapy with pemetrexed is similar to placebo, except for a small increase in loss of appetite, and significantly delayed worsening of pain and haemoptysis. In view of the improvements in overall and progression-free survival noted with pemetrexed maintenance therapy, such treatment is an option for patients with advanced non-squamous NSCLC who have not progressed after platinum-based induction therapy. Funding Eli Lilly.
Traditional, 'one size fits all' approach to chemotherapy has reached efficacy plateau. The development of molecular biomarkers is crucial for improving efficacy of therapy in patients with NSCLC.We ...review prognostic and predictive value of molecular biomarkers with special overview on biomarker-driven personalized therapy of NSCLC. Main focus is this review is on significance of EGFR mutations and ALK – EML4 alterations on due to availability of targeted drugs against these specific aberrations.
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