Lytic failure in the current pharmacointensive ST-elevated acute myocardial infarction care: insights from a pilot real-world study.

BACKGROUND: Thrombolysis remains a very acceptable reperfusion option for ST-elevated acute myocardial infarction (STEMI); however, it fails relatively frequently and unpredictably. AIM AND METHODS: To investigate correlates of lytic failure (according to the standard ST resolution criterion) in current pharmacointensive STEMI care (dual antiplatelets with antithrombin), we analyzed retrospectively clinical data and echocardiographic left ventricular systolic function before initiation of reperfusion treatment in Killip I-III STEMI patients admitted to our 'spoke' intensive cardiac care unit between 1 January and 31 December 2010. RESULTS: Of the 53 STEMI patients enrolled, 28% failed thrombolysis. Patients who did not reperfuse were less frequently active smokers (P < 0.05, odds ratio 4.33) and had a higher prevalence of hemodynamic instability [heart rate/SBP (i.e. shock index) >0.75; P < 0.05, odds ratio 13.45) and left ventricular systolic dysfunction (ejection fraction <45%; P < 0.005, odds ratio 11.14). In an exploratory multivariable logistic regression analysis, those variables were the only discriminators independently associated with lytic failure (adjusted odds ratio 8.74, 230.10, and 18.22, respectively, all P < 0.05). Moreover, the combined variables had a high accuracy for prediction of failed thrombolysis (all discriminators positive, 99% specificity and 83% positive predictive value). CONCLUSION: Our pilot study indicates that thrombolysis still fails in about one-third of STEMI patients despite the current pharmacointensive approach and suggests that failed ST resolution might be independently associated with nonsmoking habit and pretreatment hemodynamic instability and left ventricular systolic dysfunction. Larger trials are needed to verify the potential clinical implications of our preliminary observation.

Smoking cessation in patients requiring bronchoscopy: the Bronchoscopy AntiSmoking Study (BASIS).

We investigated the readiness to quit and the smoking cessation rates of smokers requiring bronchoscopy and receiving advice quitting. This randomized controlled trial evaluated the effectiveness of two smoking cessation interventions, either a brief advice (control group), or a longer support, delivered at the time of bronchoscopy. We consecutively enrolled 233 adult smokers, regardless of the initial level of motivation to quit. Their mean (SD) age was 57 (12) years; males were 192. They had smoked a median of 44.5 pack-years. Their mean (SD) Fagerstrom score was 8 (2). There was no difference between groups. Surprisingly, 45% of participants were in the action stage at baseline; these 105 subjects had quit in the week immediately prior to the bronchoscopy. At 6- and 12-months follow-up visits, respectively 41% and 29% of participants in the intervention group and 27% and 13% in the control group objectively showed a 1-week point prevalence abstinence. The difference was significant at 6 months (p<0.05) but not at 1-year visit (p=0.052), even if there was a trend towards greater cessation rate in the intervention group. In multivariable logistic models, at the final visit being a quitter was positively associated with having been in the action stage at baseline and negatively with the Fagerstrom score and the presence of smokers in household. We conclude that the time of bronchoscopy may possibly predispose smokers to quit. Further efforts are needed to clear whether more protracted support might achieve higher long-term smoking cessation rates.

The MILES-2G phase 2 study of single-agent gemcitabine with prolonged constant infusion in advanced non-small cell lung cancer elderly patients.

BACKGROUND: Gemcitabine has been widely studied in elderly patients affected by advanced non-small cell lung cancer (NSCLC). A prolonged constant infusion (10 mg/m2/min) has been proposed as a way to improve its efficacy. Aim of this study is to describe activity and toxicity of single-agent gemcitabine given as prolonged infusion in the treatment of elderly patients with advanced NSCLC. PATIENTS AND METHODS: Patients aged 70 years or older, with stage IV or IIIB (effusion/supraclavicular nodes) NSCLC, good performance status (0 or 1 according to ECOG classification) who had never received chemotherapy were eligible. Gemcitabine was administered at the dose of 1200 mg/m2 by prolonged infusion (10 mg/m2/min) on days 1 and 8 of each cycle. Courses were repeated every 21 days, for a maximum of 6 cycles, unless disease progression or severe toxicity. A single stage phase 2 design was applied, with 51 patients required to estimate a 25% +/- 10% response rate. Ten responses were required to define the treatment as active. RESULTS: Fifty-one patients were enrolled, with a median age of 76 years (range 70-83). Two complete responses and seven partial responses were observed, for an overall response rate of 17.6% (95% exact C.I.: 8.4-30.9%). The median time to disease progression was 16.1 weeks (95% C.I.: 11.1-20.6) and the median overall survival was 41.3 weeks (95% C.I.: 27.6-50.6). There were 2 toxic deaths, due to bleeding and liver toxicity, and one patient had an ischemic stroke. Other non-haematological toxicities were: fatigue (44% of patients), grade 2-3 pulmonary toxicity (8%), grade 2-3 hepatic toxicity (16%). Nausea and stomatitis were mild and no cases of cardiac toxicity were observed. Haematological toxicity was mild, with no case of febrile neutropenia. CONCLUSION: Gemcitabine at prolonged constant infusion produced a response rate lower than that required by study design and should no longer be of interest for the treatment of elderly patients with advanced NSCLC.

Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study.

PURPOSE: To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy. PATIENTS AND METHODS: Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. RESULTS: Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. CONCLUSIONS: Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

Gemcitabine, paclitaxel, and cisplatin as induction chemotherapy for patients with biopsy-proven Stage IIIA(N2) nonsmall cell lung carcinoma: a Phase II multicenter study.

BACKGROUND: The objective of the current study was to define the activity and tolerability, as well as the influence on resectability, of the combination of gemcitabine, paclitaxel, and cisplatin (GTP) as induction chemotherapy for patients with Stage IIIA(N2) nonsmall cell lung carcinoma (NSCLC). METHODS: Forty-nine chemotherapy-naïve patients (median age, 61 years; World Health Organization performance status, 0-1) with biopsy-proven Stage IIIA(N2) disease received 1000 mg/m(2) gemcitabine, 125 mg/m(2) paclitaxel, and 50 mg/m(2) cisplatin on Days 1 and 8 of every 3 weeks until reevaluation for surgery or definitive radiotherapy. RESULTS: Grade 3-4 neutropenia was the most common hematologic toxicity, occurring in 32.7% of patients; however, only 1 case of febrile neutropenia was reported. Grade 3-4 thrombocytopenia occurred in 12.2% of patients but was not associated with bleeding. Severe nonhematologic toxicities were uncommon; the only Grade 4 nonhematologic toxicity was diarrhea, which occurred in 4% of patients. One patient died after the first course of therapy, but this event was found to be unrelated to treatment. Thirty-six patients (73.5%) achieved an objective response, and an additional 4 patients had stable disease with clearance of mediastinal lymph nodes. Overall, 29 patients underwent thoracotomy and 27 (55%) underwent complete resection. Mediastinal nodes were free of tumor in 35% of all cases, and 8 pathologic complete responses (16%) were reported. Median survival was 23 months, with a 1-year survival rate of 85%. CONCLUSIONS: GTP is highly active as an induction chemotherapy regimen for Stage IIIA(N2) NSCLC and yields good toxicity results. The use of GTP in combination with radiotherapy and new biologic drugs should be explored.

Carboplatin plus vinorelbine plus G-CSF in elderly patients with extensive-stage small-cell lung cancer: a poorly tolerated regimen. Results of a multicentre phase II study.

PURPOSE AND METHODS: A multicentre phase II trial (single-stage design) was undertaken to test the activity and toxicity of carboplatin (AUC 5 according to Calvert, day 1) plus vinorelbine (25 mg/m(2) days 1 and 8) with lenograstim support, every 3 weeks in the first line treatment of elderly patients, aged 65 or more, affected by extensive small-cell lung cancer (SCLC). The primary end-point of the trial was the objective response rate. Twenty-three responses among 37 patients were considered necessary to proceed to a phase III trial. RESULTS: Twenty-eight patients were enrolled (median age 70 years). Treatment was remarkably toxic. Three patients died while on treatment. Eleven patients (39.3%, 95% exact confidence interval (CI): 21.5-59.4) had an objective response, that was complete in 2 cases. Median time to progression was 5.1 months (95% CI: 3.3-6.7). Median survival was 7.9 months (95% CI: 4.8-14.4). CONCLUSION: Carboplatin plus vinorelbine is poorly tolerated and not sufficiently active to warrant phase III comparison with standard chemotherapy regimens in elderly patients with extensive SCLC.