Efficacy and toxicity of vinorelbine-carboplatin combination in the treatment of advanced adenocarcinoma or large-cell carcinoma of the lung.

AIMS AND BACKGROUND: The aim of the study was to assess the activity and toxicity of the vinorelbine-carboplatin combination in advanced adenocarcinoma or large-cell carcinoma of the lung. The new vinca derivative, vinorelbine, shows promising activity when combined with cisplatin, but toxicity of the combination is substantial. METHODS: Accordingly, we substituted carboplatin for cisplatin in the combination in order to improve the therapeutic index. From March 1992 to March 1994, 55 untreated patients with undifferentiated unresectable or metastatic adenocarcinoma or large-cell carcinoma of the lung were recruited. The treatment consisted of a course of carboplatin (300 mg/m2) and vinorelbine (25 mg/m2) repeated every 4 weeks. The only grade 3 toxicity observed was 16 cases of grade 3 vomiting and 2 cases of grade 3 stomatitis. RESULTS: The positive response rate was 40% (partial response, 22 patients). In conclusion, the vinorelbine-carboplatin combination may be regarded as an active, safe regimen for the palliative treatment of advanced adenocarcinoma or large-cell carcinoma of the lung.

Vinorelbine monochemotherapy in non-small-cell lung cancer: experience in patients with low performance status.

The aim of this study was to investigate the activity and safety of vinorelbine in patients with low performance status. From March 1992 to June 1993 we studied 14 untreated patients with Stage IV non-small-cell lung cancer (NSCLC) and a "performance status" lower than 70% of the Karnofsky score. Treatment was by means of an intravenous administration of vinorelbine (30 mg.m-2) repeated weekly. On the whole, the toxicity was mild. Of 150 cycles administered, we observed 10 cases of Grade 3 leucopenia and 4 cases of Grade 4 leucopenia. A peripheral neurotoxicity (Grade 2-3) was reported in two patients. The objective response rate was 36% partial response. Our data suggest that vinorelbine could be an active and safe treatment for those patients who cannot receive polychemotherapy because of low performance status, and justify further larger studies comparing vinorelbine, either as a single agent or in combination, to other analogues or to assess its efficacy in supportive care.

Clinical efficacy of azithromycin in lower respiratory tract infections.

A total of 51 patients with acute exacerbation of chronic bronchitis and pneumonia were enrolled: 27 treated with azithromycin (500 mg once a day for 3 days), and 24 with roxithromycin (150 mg every 12 hours for 7 days). The two regimens were equally effective, with clinical cure in 80% and 72% of patients respectively. Bacteriological eradication on day 19-23 was obtained in 7/11 cases (64%) and in 6/13 cases (46%) in the two groups, respectively. No side effects occurred in patients treated with azithromycin, while they occurred in the roxithromycin group (2 vomiting and 1 gastritis). Clinical and bacteriological efficacy, excellent tolerability, simplified dosage (single daily dose) and short-course (3 days) therapeutic regimen make azithromycin, in our experience, efficacious for the treatment of acute exacerbation of chronic bronchitis and community-acquired pneumonia.

Immunoscintigraphy in the follow-up of patients operated on for carcinoma of the sigmoid and rectum. Preliminary report with a new monoclonal antibody: B72.3.

Thirty patients who had curative surgery for sigmoid and rectal carcinoma were studied by immunoscintigraphy using a new monoclonal antibody: B72.3 radiolabeled with Iodine-131 (I-131) or Indium-111 (In-111). Results were compared with other conventional diagnostic procedures such as computed tomography, ultrasound, endoscopy, and tumor markers. Seven patients had local recurrences and/or distant metastases. Immunoscintigraphy identified all local recurrences (five cases) that were confirmed by CT and was able to localize three of five liver metastases (two false-negatives). Furthermore, immunoscintigraphy also recorded a false-positive. Preliminary use of B72.3 shows good potential for the evaluation and detection of neoplastic sites.

Mechanical anterior resection for carcinoma of the midrectum: long-term results.

Long term results are reported on 108 patients treated by curative mechanical anterior resection for midrectum carcinoma. The functional results were good but there was a large number of local recurrences for carcinoma at Dukes C stage (28% of the total cases). Oncological results suggest that greater importance should be given to early diagnosis and to pathogenesis and risk factors for recurrence.

[Esophageal lesions caused by oral drugs. Epidemiology, physiopathologic bases, prospectives of prevention]. / Lesioni esofagee da farmaci per uso orale. Epidemiologia, basi fisiopatologiche, prospettive di prevenzione.

Esophageal injuries caused by oral medications have recently been recognized as a iatrogenic entity. This pathogenesis is due to the retention in the esophagus of drugs with caustic properties. The main predisposing factor is the practice of taking oral drugs with a small quantity of water of and/or in a recumbent position. Elderly subjects and patients with pre-existing esophageal disorders are at higher risk, so that fluid formulations or different routes of drug administration are strongly recommended. A more widespread education to the correct use of drugs and a better drug formulation are necessary for effective prevention.

Pharmacokinetic profile of fosfomycin trometamol (Monuril).

The kinetics of fosfomycin in serum and in urine was studied in 5 healthy volunteers after intravenous administration of disodium fosfomycin and after oral administration of trometamol fosfomycin at 50 mg/kg. The presence of secondary peaks in serum kinetics, more evident after oral administration, requires the use of a compartmental model with enterohepatic recirculation to which all the data of each subject were simultaneously fitted. The following values of the various pharmacokinetic parameters were calculated: central volume 10.6 +/- 0.92 liters; bioavailability 0.58 +/- 0.04; delay time in the recirculation 2.00 +/- 0.92 h; half-life 2.43 +/- 0.31 h; total clearance 8.3 +/- 1.6 l/h; urinary clearance 7.0 +/- 0.9 l/h; peak level 32.1 +/- 3.0 micrograms/ml; time of the peak 2.2 +/- 0.44 h. The fosfomycin concentration in urine remains above 1,000 micrograms/ml for 12 h and above 100 micrograms/ml for 48 h. The oral kinetics of fosfomycin is dose-dependent, as shown by serum and urine kinetics in other 4 volunteers after oral administration of 2, 3, 4 and 5 g; the fraction of the dose excreted by urine goes from 50% for 2 g to 22% for 5 g.

Effects of physical activity and diet on lipemic risk factors for atherosclerosis in women.

Serum lipoproteins were studied in active and sedentary young women. The groups were matched for age, body weight, and blood pressure. A quantitative and qualitative evaluation of the diet was performed. In spite of a higher intake of saturated fat and cholesterol, serum concentrations of triglyceride, total cholesterol, and low-density lipoprotein cholesterol in the active group were not significantly different from the controls. Nevertheless, high-density lipoprotein cholesterol (HDL-C) levels were significantly higher in the active subjects even after covariance adjustment for nutrient intake; therefore, the HDL-C increase seems to depend on physical activity "per se" rather than on differences in diet.

Pseudomonas septicaemia. A review of 60 cases observed in a university hospital.

Epidemiological, clinical features and the pathogenesis of 60 cases of pseudomonas septicaemia, observed over a period of 7 years from 1975 to 1981, are described. The mean frequency of occurrence was 0.40 episodes per 1000 admissions and an incidence of 66 per cent was observed in patients with serious underlying diseases, such as haematological malignancies and neoplasia. Thirty-seven patients had received cytotoxic and immunosuppressive therapy and showed a marked leukopenia, and whenever the leukocyte count fell below 2000/mm3, the prognosis was significantly worse. The most common portals of entry were the respiratory and gastrointestinal tracts. The overall mortality was very high (75 per cent) and mainly related to septic shock. Apart from the very high frequency of this complication (24 patients, 40 per cent of all cases), a typical clinical picture, distinguishing pseudomonas from other Gram-negative septicaemias, did not emerge.

Exocrine pancreatic function in diabetic rats treated with intraportal islet transplantation.

Streptozotocin-diabetic rats with chronic pancreatic fistula show severe impairment of secretin-stimulated pancreatic secretion while the action of pancreozymin remains unchanged. Intrahepatic transplantation of islets of Langerhans restores the response of ductal cells to secretin; physiological control of insulin secretion appears to be essential for exocrine function.