Respiratory infections and asthma.

Clinical and experimental evidence suggests an important role for respiratory infections in the development of asthma attacks. Viral upper respiratory infections have been associated with 80% of asthma exacerbations in children and 50% of all asthma episodes in adults. Human rhinovirus has been implicated as the principal virus associated with asthma episodes. Separate studies indicate that atypical bacteria such as Chlamydia pneumoniae and Mycoplasma pneumoniae may precipitate asthma symptoms. Although not completely clarified, the intricate pathogenetic mechanisms by which viral infections promote asthma attacks have been extensively investigated in recent years. By contrast, it has not yet been established whether atypical bacterial infections are an epiphenomenon or a pathogenic event in asthma.

Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group.

PURPOSE: In our previous phase II study, the cisplatin, gemcitabine, and vinorelbine (PGV) regimen produced a median survival time (MST) of approximately 1 year in advanced non-small-cell lung cancer (NSCLC) patients. The present study was aimed at comparing the MST of patients treated with this triplet regimen with the MSTs of patients receiving cisplatin and vinorelbine (PV) or cisplatin and gemcitabine (PG). PATIENTS AND METHODS: From April 1997, patients with locally advanced or metastatic NSCLC, an age of < or = 70 years, and an Eastern Cooperative Oncology Group performance status < or = 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m(2), gemcitabine 1,000 mg/m(2), and vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m(2) on day 1 and gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m(2) on days 1 and 29 and vinorelbine 30 mg/m(2)/wk (arm C). According to the two-stage design for phase III trials, an interim analysis was planned when the first 60 patients per arm were assessable for survival. RESULTS: The survival data of 180 NSCLC patients (stage IIIB, 76 patients; stage IV, 104 patients) were analyzed in April 1999. Overall, 128 patients had died (PGV, n = 33; PG, n = 42; and PV, n = 53). The MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively, and the corresponding 1-year projected survival rates were 45%, 40%, and 34%, respectively. When only patients with stage IV disease were considered, an even stronger difference was seen between PGV (MST = 47 weeks) and both PG (34 weeks) and PV (27 weeks). At multivariate Cox analysis, the estimate hazard of death for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence interval, 0.16 to 0.77; P <.01). The response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm. Both hematologic and nonhematologic toxicities were not substantially worse in patients who received the PGV regimen. CONCLUSION: The PGV regimen is associated with a substantial survival gain (MST > 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.

Interim analysis of a phase III trial comparing cisplatin, gemcitabine, and vinorelbine vs. either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non small-cell lung cancer. A Southern Italy Cooperative Oncology Group Study.

In a previous phase II randomized study, a cisplatin/gemcitabine/vinorelbine (PGV) regimen produced a 50-week median survival time (MST) in advanced non small-cell lung cancer (NSCLC) patients. The present trial was planned to randomly compare the outcome of patients treated with this new triplet regimen with those of patients receiving either cisplatin plus vinorelbine (PV) or cisplatin plus gemcitabine (PG) doublet combinations. One hundred eighty patients with stage IIIB (76) or IV (104) disease, aged

Cisplatin, gemcitabine, and paclitaxel in locally advanced or metastatic non-small-cell lung cancer: a phase I-II study. Southern Italy Cooperative Oncology Group.

PURPOSE: Because both cisplatin-paclitaxel and cisplatin-gemcitabine combinations are generally considered to be among the most active regimens in non-small-cell lung cancer (NSCLC) patients, this study aimed to determine the maximum-tolerated dose (MTD) of paclitaxel when combined with fixed doses of cisplatin and gemcitabine in advanced NSCLC patients and aimed to define the therapeutic activity of this new regimen. PATIENTS AND METHODS: From October 1996 to September 1998, 75 patients with stage IIIB-IV NSCLC, who were either chemotherapy-naive (65 patients) or who had been pretreated (10 patients), received fixed doses of cisplatin (50 mg/m(2)) and gemcitabine (1,000 mg/m(2)) and escalating doses of paclitaxel in a 1-hour infusion, all on days 1 and 8, every 3 weeks. RESULTS: Five different paclitaxel doses were tested, for a total of 275 cycles delivered. The escalation was stopped at the paclitaxel dose of 75 mg/m(2) in pretreated patients, whereas it continued to 150 mg/m(2) in chemotherapy-naive patients. A total of 65 chemotherapy-naive patients were treated. A paclitaxel dose of 125 mg/m(2) was recommended for phase II, and a total of 39 patients were treated at this level, for a total of 158 cycles delivered. No treatment-related deaths occurred. Five patients were hospitalized because of sepsis, and packed RBC transfusion was required in 13 patients. Grade 4 neutropenia and thrombocytopenia occurred in 23 (31%) and eight (11%) patients, respectively. Overall, 74 of the 75 patients were assessable for response. Four complete (CR) and 38 partial (PR) responses were recorded, for an overall response rate (ORR) of 57%. Three of the ten pretreated patients achieved a PR, compared with four CRs and 35 PRs in the 64 chemotherapy-naive patients (ORR, 61%). Thirty-eight of 39 patients included in phase II were assessable for response and quality of life (QOL) (one patient's disease was not measurable). Two CRs and 24 PRs were recorded in this group, for an ORR of 68% (95% confidence interval, 51% to 82%). The QOL score improved in 27 of 38 (71%) patients. The median survival time was 15 months in the 65 chemotherapy-naive patients, but it had not yet been reached in the 39 patients included in phase II, for whom the 1-year projected survival was 70%. CONCLUSION: The cisplatin-gemcitabine-paclitaxel combination is a feasible and well-tolerated approach in advanced NSCLC patients. Both a major response and a QOL improvement can be obtained in a high proportion of patients, with a median survival time exceeding 1 year. A phase III trial comparing this combination with other effective regimens is under way.

Viruses and asthmatic syndromes.

Viruses are recognized to be the major cause of respiratory infections. Clinical and experimental evidence also supports an important role for viruses in the pathogenesis of lower airway disease and asthma exacerbation. In prospective epidemiological studies, 80% of asthma exacerbations in school-aged children and half of all asthma exacerbations in adults have been associated with viral upper respiratory infections. Human rhinovirus (HRV) has been implicated as the principal virus associated with asthma exacerbation. In our studies on respiratory viruses, we have observed two clinical patterns of presentation. The viruses can either be a precipitating factor of respiratory illness characterized by a typical clinical onset, or can induce an atypical clinical onset such as haemoptysis, pleuritis, spontaneous pneumothorax and asthmatic syndrome. Thus the observed clinicoradiological and functional features during atypical viral respiratory infection may be correlated to the long-term biological effects induced by previous and concurrent infections.

Partial substitution of cisplatin with carboplatin in combination with etoposide in advanced non-small cell lung cancer (NSCLC): a multicentric randomised phase II trial.

Seventy previously untreated patients with advanced NSCLC were randomised, after stratification for stage (IIIB vs. IV) and Performance Status (0-1 vs. 2), to receive either treatment A: CDDP 40 mg/m2 + VP16 100 mg/m2 day 1-3 (37 patients); or treatment B: CBDCA 250 mg/m2 day 1 + CDDP 30 mg/m2 day 2, 3 + VP16 100 mg/m2 day 1-3 (33 patients). Therapy was recycled on day 29 in both arms. The two arms were well balanced for the main pretreatment characteristics. Sixty-six patients (32 with Stage IIIB and 34 with Stage IV disease) were evaluable for toxicity and response (arm A = 34, arm B = 32), while four ineligible patients were excluded from analysis. Acute toxicity was assessed at recycling. Non-hematologic toxicity was higher in arm A. However, the reduction of nephrotoxicity (9% vs. 23%) in arm B was lower than expected. Leukopenia (15 vs. 5 patients) or thrombocytopenia (7 vs. 0 patients) of any grade affected more patients of arm B. Moreover, Grade 3-4 leukopenia (six patients) or thrombocytopenia (four patients) was observed only in arm B. Seventeen patients responded: 11/34 (32%; 95% C.I. = 17-50%) in arm A, and 6/32 (19%; 95% C.I. = 7-36%) in arm B. Median survival times of 40 and 34 weeks, respectively, were reported in arm A and B. Stage IIIB and squamous cell histology were associated with a higher probability of response. In conclusion, the partial replacement of CDDP with CBDCA in combination with VP16 slightly improves the tolerance of the treatment in terms of nephro- and neurotoxicity; however, it induces a significant increase in hematologic toxicity. In view of this unfavourable toxicologic profile and of the discouraging response rate observed, this regimen cannot be recommended as standard treatment in advanced NSCLC.

Pefloxacin in lower respiratory tract infections.

To determine the efficacy and safety of pefloxacin in the treatment of lower respiratory tract infections, a multicentre trial involving four departments of respiratory diseases was performed. One hundred and eight patients were admitted to the study: most of them were affected with exacerbations of chronic bronchitis or with pneumonia complicating lung cancer. Isolation and identification of responsible microorganisms from bronchial secretions was possible in 78 patients. Seven patients were withdrawn, one for worsening of the underlying disease and six for early side-effects. Thus, of 108 patients recruited, 101 completed the course of therapy (pefloxacin 400 mg bd for 5-14 days) and could be submitted to final evaluation. Of these 43 (42.6%) were cured and 48 (47.5%) showed improvement. Eradication of responsible microorganisms was achieved in 70 (90.9%) of 77 patients microbiologically evaluated. Side-effects of moderate severity were observed in 12 patients (gastrointestinal disturbances in 11 and dyspnoea in one); these did not necessitate discontinuation of therapy.

[Pefloxacin in the treatment of lower respiratory tract infections]. / La pefloxacina nel trattamento delle infezioni delle basse vie respiratorie.

Pefloxacin is an antibacterial agent belonging to the group of quinolones having a methyl-carboxylic acid which possesses a high activity as compared to other quinolonic drugs. In this study we tested the efficacy and tolerability of the drug in the treatment of 25 patients with environmental L.R.T.I. (Low Respiratory Tract Infections). The microbiological and clinical characteristics of the drug were tested in this study. Excellent results were obtained in 96% of the patients treated and the tolerability was also very good.

[Pentoxifylline in the blood rheological and coagulative changes in chronic respiratory failure]. / La pentossifillina nelle alterazioni emoreologiche e coagulative dell'insufficienza respiratoria cronica.

In this study, some hemorheological and coagulative parameters (blood viscosity, erythrocyte filtrability, CPA, platelet aggregation) have been evaluated in 40 patients with Chronic Respiratory Failure. The results obtained document in these patients, important hemorheologic changes. 11 patients with most serious rheologic changes have been treated with Pentossifillina. A significative improvement of the explored parameters and of the clinical condition has been checked after treatment.

Comparative clinical evaluation of ceftriaxone in treating lower respiratory tract infections.

To evaluate the clinical and microbiological efficacy and safety of ceftriaxone in comparison with cefotaxime in treating acute lower respiratory tract infections two open randomized trials were performed. Sixty-two adult hospital in-patients were entered and 58 completed the study. The patients suffered from either acute (broncho-)pneumonia (19pts) or severe exacerbation of chronic bronchopneumonia (39 pts). Forty-one of the patients had severe underlying or concurrent diseases. Diagnoses were in all cases confirmed by isolation of the causative pathogen(s) from bronchial brushing or washing under fiberoptic bronchoscopy. Twenty-eight patients were administered at random with either a single 2g daily dose of ceftriaxone or 2g twice daily dose of cefotaxime (1st trial). Successively (2nd trial) ceftriaxone was administered at a dose of 1g once daily either i.v. or i.m. The duration of treatment ranged from 7 to 12 days. A satisfactory response was observed in all patients suffering from acute pneumonia or bronchopneumonia; the eradication rate of the causative pathogen was 73% and 62% for ceftriaxone and cefotaxime, respectively. Concerning the exacerbation of chronic bronchopneumonia (39 patients) an overall satisfactory response to both treatments was registered in about 80% of cases. No significant differences between the 1g and 2g single daily dosing regimens of ceftriaxone appeared. Both ceftriaxone and cefotaxime were well tolerated: no or minimal changes in laboratory values were noticed. It is concluded that a 1g or 2g single daily dose of ceftriaxone were at least as effective as a 2g twice daily dose of cefotaxime in treating acute lower respiratory tract infections due to susceptible pathogens.

Treatment of lower respiratory tract infections with ceftriaxone and cefotaxime. A comparative study.

The microbiological and clinico-therapeutic efficacy and safety of ceftriaxone were compared with those of cefotaxime in an open randomized trial. Fifty-four adult hospitalized patients (37 males and 17 females) suffering from either acute bronchopneumonia (19) or acute exacerbations of chronic bronchopneumonia (35) have been investigated. Four patients were withdrawn from the trial. Underlying diseases were present in 41 patients. Ceftriaxone was administered at a once-a-day dose of either 1 or 2 g (in 13 and 14 patients, respectively) and cefotaxime at a 2 g twice daily dosing regimen (27 patients), both antibiotics being given for 7-12 days. In the ceftriaxone group, 15 out of the 27 patients were cured (55%) and 9 had a favourable clinical response for a total satisfactory response rate of 88%. The causative pathogen was eliminated in 18 (66%) patients. The results obtained in the cefotaxime group did not differ significantly, but 2 patients were excluded from the study because of in vitro resistance of the causative pathogen isolated. Both drugs were well tolerated: no relevant laboratory changes were registered. The results indicate that ceftriaxone at a dosage of 2 or 1 g daily is at least as effective as cefotaxime given daily at a dosage of 4 g in the treatment of severe lower respiratory tract infections.