COMET: a multicomponent home-based disease-management programme versus routine care in severe COPD.

The COPD Patient Management European Trial (COMET) investigated the efficacy and safety of a home-based COPD disease management intervention for severe COPD patients.The study was an international open-design clinical trial in COPD patients (forced expiratory volume in 1 s <50% of predicted value) randomised 1:1 to the disease management intervention or to the usual management practices at the study centre. The disease management intervention included a self-management programme, home telemonitoring, care coordination and medical management. The primary end-point was the number of unplanned all-cause hospitalisation days in the intention-to-treat (ITT) population. Secondary end-points included acute care hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and exercise) index and exacerbations. Safety end-points included adverse events and deaths.For the 157 (disease management) and 162 (usual management) patients eligible for ITT analyses, all-cause hospitalisation days per year (mean±sd) were 17.4±35.4 and 22.6±41.8, respectively (mean difference -5.3, 95% CI -13.7 to -3.1; p=0.16). The disease management group had fewer per-protocol acute care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a lower mortality rate (1.9% versus 14.2%; p<0.001), with no difference in exacerbation frequency. Patient profiles and hospitalisation practices varied substantially across countries.The COMET disease management intervention did not significantly reduce unplanned all-cause hospitalisation days, but reduced acute care hospitalisation days and mortality in severe COPD patients.

Doxycycline for prevention of erlotinib-induced rash in patients with non-small-cell lung cancer (NSCLC) after failure of first-line chemotherapy: A randomized, open-label trial.

BACKGROUND: Rash is a common epidermal growth factor receptor inhibitor-induced toxicity that can impair quality of life and treatment compliance. OBJECTIVE: We sought to evaluate the efficacy of doxycycline in preventing erlotinib-induced rash (folliculitis) in patients with non-small-cell lung cancer. METHODS: This open-label, randomized, prospective, phase II trial was conducted in 147 patients with locally advanced or metastatic non-small-cell lung cancer progressing after first-line chemotherapy, randomized for 4 months with erlotinib alone 150 mg/d per os (control arm) or combined with doxycycline 100 mg/d (doxycycline arm). Incidence and severity of rash, compliance, survival, and safety were assessed. RESULTS: Baseline characteristics of the 147 patients were well balanced in the intent-to-treat population. Folliculitis occurred in 71% of patients in the doxycycline arm and 81% in the control arm (P = .175). The severity of folliculitis and other skin lesions was lower in the doxycycline arm compared with the control arm. Other adverse events were reported at a similar frequency across arms. There was no significant difference in survival between treatment arms. LIMITATIONS: The open-label design of the study and the duration of the treatment with doxycycline are limitations. CONCLUSION: Doxycycline did not reduce the incidence of erlotinib-induced folliculitis, but significantly reduced its severity.

A clinical in-hospital prognostic score for acute exacerbations of COPD.

BACKGROUND: The use of a severity score to help orientation decisions could improve the efficiency of care for acute exacerbations of COPD (AECOPD). We previously developed a score ('2008 score', based on age, dyspnea grade at steady state and number of clinical signs of severity) predicting in-hospital mortality in patients with AECOPD visiting emergency departments (EDs). External validity of this score remained to be assessed. OBJECTIVES: To test the predictive properties of the '2008 score' in a population of patients hospitalized in medical respiratory wards for AECOPD, and determine whether a new score specifically derived from this population would differ from the previous score in terms of components or predictive performance. METHODS: Data from a cohort study in 1824 patients hospitalized in a medical ward for an AECOPD were analyzed. Patients were categorized using the 2008 score and its predictive characteristics for in-hospital mortality rates were assessed. A new score was developed using multivariate logistic regression modeling in a randomly selected derivation population sample followed by testing in the remaining population (validation sample). Robustness of results was assessed by case-by-case validation. RESULTS: The 2008 score was characterized by a c-statistic at 0.77, a sensitivity of 69% and a specificity of 76% for prediction of in-hospital mortality. The new score comprised the same variables plus major cardiac comorbidities and was characterized by a c-statistic of 0.78, a sensitivity of 77% and specificity of 66%. CONCLUSIONS: A score using simple clinical variables has robust properties for predicting the risk of in-hospital death in patients hospitalized for AECOPD. Adding cardiac comorbidities to the original score increased its sensitivity while decreasing its specificity.

High-risk patients following hospitalisation for an acute exacerbation of COPD.

The aim of this study was to assess long-term mortality and predictive factors of death after hospital admission for acute exacerbation of chronic obstructive pulmonary disease (COPD). 1824 patients (23.2% female; mean age 70.3±11.3 years) consecutively admitted for acute exacerbation of COPD in the respiratory medicine departments of 68 general hospitals between October 2006 and June 2007 were prospectively enrolled in a follow-up cohort. Their vital status was documented between October 2010 and April 2011. Vital status was available for 1750 patients (95.9%), among whom 787 (45%) died during follow-up. Multivariate analysis found that age (60-80 years and ≥80 years versus <60 years, relative risk 2.99, 95% CI 2.31-3.89), lower body mass index (25-30 kg·m(-2) versus ≤20 kg·m(-2), relative risk 0.80, 95% CI 0.66-0.97), lung cancer (relative risk 2.08, 95% CI 1.43-3.01), cardiovascular comorbidity (relative risk 1.35, 95% CI 1.16-1.58), previous hospital admissions for acute exacerbation of COPD (four or more versus none, relative risk 1.91, 95% CI 1.44-2.53), use of accessory respiratory muscles (relative risk 1.19, 95% CI 1.01-1.40) or lower-limb oedema (relative risk 1.74, 95% CI (1.44-2.12)) at admission and treatment by long-term oxygen therapy at discharge (relative risk 2.09, 95% CI 1.79-2.45) were independent risk factors of death. Mortality rate during the 4 years following hospital admission for acute exacerbation of COPD was high (45%). Simple clinical information relating to respiratory and general status can help in identifying high-risk patients and targeting more intensive follow-up and care. Interestingly, cardiovascular comorbidities and past hospitalisations for acute exacerbation of COPD, but not forced expiratory volume in 1 s, independently predicted the risk of death.

Induction or consolidation chemotherapy for unresectable stage III non-small-cell lung cancer patients treated with concurrent chemoradiation: a randomised phase II trial GFPC - IFCT 02-01.

PURPOSE: The objective of this randomised phase II study was to evaluate the impact in terms of response and toxicities of induction or consolidation chemotherapy respectively before or after concurrent chemoradiotherapy in unresectable stage III non-small-cell lung cancer. PATIENTS AND METHODS: In the induction arm, patients received induction chemotherapy with cisplatin (80 mg/m(2)) and paclitaxel (200 mg/m(2)) on days 1 and 29 followed by a concurrent chemoradiotherapy (66 Gy in 33 fractions, cisplatin 80 mg/m(2) days 1, 29 and 57, vinorelbine 15 mg/m(2) days 1, 8, 29, 36, 57 and 64). In consolidation arm, the same concurrent chemoradiotherapy began on day 1 followed by two cycles of cisplatin and paclitaxel. RESULTS: One hundred twenty seven patients were randomised. The intent to treat response rates in induction and consolidation arms were 58% and 56% respectively. Median survival was 19.6 months in induction arm and 16.3 months in consolidation arm and 4-year survival rates were 21% and 30% respectively. Haematologic and non-haematologic toxicities were similar in both arms, except grade 3/4 oesophagitis, more frequent in consolidation arm than in induction arm (17% versus 10%). CONCLUSION: Cisplatin-based chemotherapy as induction or consolidation with concurrent chemoradiotherapy can be administrated safely. Response rates were similar in both arms with a trend in favour for consolidation arm for long-term survival.

Oral vinorelbine and cisplatin with concurrent radiotherapy after induction chemotherapy with cisplatin and docetaxel for patients with locally advanced non-small cell lung cancer: the GFPC 05-03 study.

INTRODUCTION: The aim of this multicenter phase II trial was to evaluate the combination of oral vinorelbine and cisplatin with radiotherapy (RT) after cisplatin-docetaxel induction chemotherapy (CT) in patients with locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with previously untreated, inoperable, histologically or cytologically confirmed stage IIIA or IIIB NSCLC, with performance status ≤ 1 and weight loss ≤ 10% received two cycles of induction CT with cisplatin (75 mg/m) and docetaxel (75 mg/m) every 3 weeks. Patients with a tumor response or stabilization continued to receive cisplatin (80 mg/m) and oral vinorelbine (40 mg/m) on days 1 and 8 for two cycles, with concomitant thoracic RT (2 Gy/d, 5 d/wk, and total dose 66 Gy). RESULTS: Fifty-six patients were enrolled. All patients (n = 38) who received CT-RT were assessable for the tumor response. There were no complete responses. In the intent-to-treat analysis, the response rates were 32.1% after induction CT and 41.1% after CT-RT. The median progression-free and overall survival times were 9.2 months (95% confidence interval: 7-14) and 20.8 months (95% confidence interval: 13.7-24.1), respectively. Adverse effects of RT-CT were grades 3 to 4 neutropenia (four patients) and grade 3 esophageal toxicity (one patient). No treatment-related deaths occurred. CONCLUSION: The oral vinorelbine-cisplatin combination with concurrent RT is feasible and has a favorable risk-benefit ratio in stage IIIA/IIIB NSCLC.