Maintenance chemotherapy in advanced non-small-cell lung cancer.

Lancet Oncol. 2012 Mar;13(3):217-8

Authors: Jassem J

PMID: 22341743 [PubMed - indexed for MEDLINE]

Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial.

Lancet Oncol. 2012 Mar;13(3):247-55

Authors: Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C

Abstract
BACKGROUND: Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) benefit from pemetrexed maintenance therapy after induction therapy with a platinum-containing, non-pemetrexed doublet. The PARAMOUNT trial investigated whether continuation maintenance with pemetrexed improved progression-free survival after induction therapy with pemetrexed plus cisplatin.
METHODS: In this double-blind, multicentre, phase 3, randomised placebo-controlled trial, patients with advanced non-squamous NSCLC aged 18 years or older, with no previous systemic chemotherapy for lung cancer, with at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 participated. Before randomisation, patients entered an induction phase which consisted of four cycles of induction pemetrexed (500 mg/m(2)) plus cisplatin (75 mg/m(2)) on day 1 of a 21-day cycle. Patients who did not progress after completion of four cycles of induction and who had an ECOG performance status of 0 or 1 were stratified according to disease stage (IIIB or IV), ECOG performance status (0 or 1), and induction response (complete or partial response, or stable disease), and randomly assigned (2:1 ratio) to receive maintenance therapy with either pemetrexed (500 mg/m(2) every 21 days) plus best supportive care or placebo plus best supportive care until disease progression. Randomisation was done with the Pocock and Simon minimisation method. Patients and investigators were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00789373.
FINDINGS: Of the 1022 patients enrolled, 939 participated in the induction phase. Of these, 539 patients were randomly assigned to receive continuation maintenance with pemetrexed plus best supportive care (n=359) or with placebo plus best supportive care (n=180). Among the 359 patients randomised to continuation maintenance with pemetrexed, there was a significant reduction in the risk of disease progression over the placebo group (HR 0·62, 95% CI 0·49-0·79; p<0·0001). The median progression-free survival, measured from randomisation, was 4·1 months (95% CI 3·2-4·6) for pemetrexed and 2·8 months (2·6-3·1) for placebo. Possibly treatment-related laboratory grade 3-4 adverse events were more common in the pemetrexed group (33 [9%] of 359 patients) than in the placebo group (one [<1%] of 180 patients; p<0·0001), as were non-laboratory grade 3-5 adverse events (32 [9%] of 359 patients in the pemetrexed group; eight [4%] of 180 patients in the placebo group; p=0·080); one possibly treatment-related death was reported in each group. The most common adverse events of grade 3-4 in the pemetrexed group were anaemia (16 [4%] of 359 patients), neutropenia (13 [4%]), and fatigue (15 [4%]). In the placebo group, these adverse events were less common: anaemia (one [<1%] of 180 patients), neutropenia (none), and fatigue (one <1%]). The most frequent serious adverse events were anaemia (eight [2%] of 359 patients in the pemetrexed group vs none in the placebo group) and febrile neutropenia (five [1%] vs none). Discontinuations due to drug-related adverse events occurred in 19 (5%) patients in the pemetrexed group and six (3%) patients in the placebo group.
INTERPRETATION: Continuation maintenance with pemetrexed is an effective and well tolerated treatment option for patients with advanced non-squamous NSCLC with good performance status who have not progressed after induction therapy with pemetrexed plus cisplatin.
FUNDING: Eli Lilly and Company.

PMID: 22341744 [PubMed - indexed for MEDLINE]

Sputum purulence-guided antibiotic use in hospitalised patients with exacerbations of COPD.

Eur Respir J. 2012 Apr 20;

Authors: Soler N, Esperatti M, Ewig S, Huerta A, Agustí C, Torres A

Abstract
In patients with acute exacerbations of COPD needing hospitalisation, sputum purulence is associated with bacteria in the lower respiratory tract. We performed a pilot-study applying sputum purulence-guided strategy of antibiotic treatment and investigating the relationship between sputum purulence and biomarkers.Prospective non-randomised interventional pilot study. In hospitalised patients with acute exacerbation of COPD antibiotics were restricted to those with purulent sputum. Primary endpoint was rate of therapeutic failure during hospitalisation. Secondary endpoints were parameters reflecting short- and long-term outcomes.We included 73 patients, 34 with non-purulent sputum. No differences were observed on therapeutic failure criteria (9% non-purulent versus 10% purulent [p=0.51]). Serum C reactive protein (CRP) was significant increased in the purulent group at admission (11.6 versus 5.3, p=0.006) and at day 3 (2.7 versus 1.2, p=0.01). Serum procalcitonin (PCT) was similar between the groups. No differences were found in short-term outcomes. The exacerbation rate at 180 days was higher in the purulent group.These results support the hypothesis of performing a randomised trial using sputum purulence-guided antibiotic treatment strategy in patients with acute exacerbations of COPD. CRP but not PCT may be a useful parameter to increase confidence about the absence of bacterial bronchial infection.

PMID: 22523352 [PubMed - as supplied by publisher]

Clinical and inflammatory determinants of bronchial hyperresponsiveness in COPD.

Eur Respir J. 2012 Apr 20;

Authors: van den Berge M, J M Vonk , Gosman M, Lapperre TS, Snoeck-Stroband JB, Sterk PJ, Kunz LI, Hiemstra PS, Timens W, Ten Hacken NH, Kerstjens HA, Postma DS

Abstract
Bronchial hyperresponsiveness (BHR) is regarded as a hallmark of asthma, yet it is also present in a considerable number of COPD patients. Epidemiological studies have shown that BHR provides complementary information to FEV1 for development and progression of COPD. We hypothesized that the severity of BHR and its longitudinal changes associate with both clinical and airway inflammation measures in COPD. Our hypothesis was tested in 114 COPD patients (median age 62.9 years, packyears 45.9) participating in the GLUCOLD study, previously showing an improvement in BHR with fluticasone and fluticasone/salmeterol. At baseline, and 6 and 30 months after treatment, we investigated lung function, including body plethysmography, PC20 methacholine, sputum induction, and bronchial biopsies. By performing both cross-sectional and longitudinal analyses, we showed that BHR in COPD is predominantly associated with residual volume/total lung capacity, a measure of air trapping, and airway inflammation reflected by the number of neutrophils, macrophages, and lymphocytes in sputum and bronchial biopsies. Our findings indicate that BHR is an independent trait in COPD and provides important information on phenotype heterogeneity and disease activity.

PMID: 22523354 [PubMed - as supplied by publisher]