Gemcitabine, ifosfamide, and cisplatin combination (GIP) in treatment of patients with locally advanced or metastatic nonsmall cell lung cancer: results of a phase II study.

OBJECTIVES: We have carried out a phase II study to evaluate the efficacy and the toxicity associated with the combination of gemcitabine, ifosfamide, and cisplatin (GIP) in chemotherapy-naive patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: Each cycle consisted of treatment with ifosfamide (3000 mg/m2) and gemcitabine (1500 mg/m2) on day 1, followed by cisplatin (100 mg/m2) and gemcitabine (1500 mg/m2) on day 15. Each treatment cycle was repeated every 28 days. A maximum of 6 cycles were administered. RESULTS: Sixty NSCLC patients (23 stage III and 37 stage IV) were entered in this study. The median survival for all patients is 9 months (stage III: 12.3 months; stage IV: 7.5 months). The overall survival at 1 and 2 years is 38% and 17%, respectively (52% and 30% for stage III; 30% and 8% for stage IV). The median time to progression is 6.3 months (stage III: 8.8 months; stage IV: 3.6 months). Progression free survival at 1 and 2 years for all patients is 22% and 8%. The response rate is 56% for patients with stage III disease and 27% for patients with stage IV disease. Among the grade 3/4 toxicities, hematological toxicity was the most frequent (59% of patients) followed by gastrointestinal toxicity (nausea/vomiting) in 21% of patients. CONCLUSION: The GIP combination yields an efficacy, in terms of response and survival, comparable to that reported with other triplet combination treatments for local advanced or metastatic NSCLC, with an acceptable toxicity profile.

Steady-state trough serum and epithelial lining fluid concentrations of teicoplanin 12 mg/kg per day in patients with ventilator-associated pneumonia.

OBJECTIVE: To determine the steady-state trough serum and epithelial lining fluid (ELF) concentrations of teicoplanin 12 mg/kg per day in critically ill patients with ventilator associated pneumonia. DESIGN AND SETTING: Prospective, pharmacokinetic study in the surgical intensive care unit in a university hospital. PATIENTS: Thirteen adult patients with nosocomial bacterial pneumonia on mechanical ventilation were enrolled. INTERVENTIONS: All subjects received a 30-min intravenous infusion of 12 mg/kg teicoplanin every 12 h for 2 consecutive days followed by 12 mg/kg once daily. Teicoplanin concentrations in serum and ELF were determined simultaneously 4-6 days after antibiotic administration started. MEASUREMENTS AND RESULTS: The median total and free concentrations of teicoplanin in serum at trough were 15.9 microg/ml (range 8.8-29.9) and 3.7 (2.0-5.4), respectively. The concentration in ELF was 4.9 (2.0-11.8). CONCLUSIONS: In critically ill patients with ventilator-associated pneumonia the administration of high teicoplanin doses is required to reach sufficient trough antibiotic concentrations in lung tissues at steady state. At that time trough-free concentrations of teicoplanin in serum and ELF are comparable.

Comparison of nebulized epinephrine and terbutaline in patients with acute severe asthma: a controlled trial.

PURPOSE: To compare the efficacy and tolerability of nebulized adrenaline and terbutaline in acute severe asthma. DESIGN: Prospective pilot randomized double-blind cross-over trial. SETTING: Emergency department of a university hospital. PATIENTS: Thirty-eight patients admitted with severe acute asthma. Each patient received adrenaline (3 mg) and terbutaline (5 mg) nebulizations over 20 min in randomized order. Additional treatment comprised methylprednisolone, intravenous hydration, and oxygen. The efficacy and tolerability of the two drugs were evaluated at the end of each nebulization as well as potential synergistic effects. RESULTS: Eighteen patients received adrenaline first, and 20 received terbutaline first. Peak expiratory flow (PEF) improved significantly in both groups after the first nebulization (from 157 L/min +/- 111 L/min to 199 L/min +/- 134 L/min with adrenaline, P <.01; and from 142 L/min +/- 65 L/min to 193 L/min +/- 181 L/min with terbutaline, P <.01). Both drugs induced a significant decrease in respiratory frequency. The improvement in PaO2 was only significant with terbutaline. Respiratory frequency, PEF and PaO2 were not improved by the second nebulization. No adverse effects were observed. CONCLUSIONS: Adrenaline nebulization was as effective and as well tolerated as terbutaline in acute severe asthma. No synergistic effect between terbutaline and adrenaline was observed.

Colonization of lower respiratory tract with anaerobic bacteria in mechanically ventilated patients.

OBJECTIVE: To study lower respiratory tract colonization by anaerobic bacteria in ICU patients on prolonged mechanical ventilation using two types of protected tracheal sampling methods. DESIGN AND SETTING: Prospective clinical investigation in the intensive care unit of a university hospital. PATIENTS: Twenty-six consecutive patients mechanically ventilated within 24 h after their admission in ICU and with expected duration of mechanical ventilation longer than 7 days. MEASUREMENTS AND RESULTS: Two types of protected tracheal sampling methods were obtained without the use of bronchoscopic guidance on the day following intubation and twice a week until extubation: protected tracheal aspiration and protected tracheal specimen brush. Specific methods for anaerobic isolation were used. Early colonization was defined if colonization occurred within the first 5 days after intubation. Of the 26 patients studied 22 were colonized by at least one bacterial strain. Twenty-one patients were colonized by aerobic and 15 by anaerobic bacteria. Twenty-eight anaerobic strains were identified, with bacterial counts higher than 10(3) cfu/ml in 11 cases. Of the 15 patients colonized by anaerobes 14 were also colonized by aerobic bacteria. The use of protected specimens ruled out oropharyngeal contamination. Early onset colonization occurred in 16 of 22 patients colonized by aerobes and in 8 of 15 patients colonized by anaerobes. Five patients developed ventilatory-acquired pneumonia following colonization (by anaerobic bacteria in two cases). In eight patients colonization by anaerobic bacteria occurred despite antimicrobial therapy. CONCLUSIONS: These results show that anaerobic bacteria frequently colonize the lower respiratory tract of mechanically ventilated patients and underline the potential importance of the anaerobic bacteria in ventilatory acquired pneumonia.