Masaharu Nagayama

Plasminogen activators and their inhibitors in non‐small cell lung cancer. Low content of type 2 plasminogen activator inhibitor associated with tumor dissemination

Background. Evidence suggests that plasminogen activators and their inhibitors play an important role in tumor spread.

Phase II study of combination chemotherapy with S-1 and weekly cisplatin in patients with previously untreated advanced non-small cell lung cancer

We aimed to evaluate the efficacy and safety of combination chemotherapy with S-1 and low-dose weekly cisplatin in patients with advanced non-small cell lung cancer (NSCLC). In this phase II trial, previously untreated patients with stage IIIB/IV NSCLC were treated with oral administration of S-1 at 80 mg/m(2) for 21 days and three consecutive weekly low doses of cisplatin (25 mg/m(2)) followed by a 2-week rest period. Twenty-six patients were eligible for the assessment of efficacy and safety. Six partial responses were observed with an overall response rate of 23.1% (95% confidence interval: 12.3-31.6%). The median survival time and median progression-free survival were 13.4 months and 5.4 months, respectively. Grade 3/4 hematologic toxicities were observed in 9 patients (34.6%), including one grade 4 neutropenia and thrombocytopenia. As for non-hematologic adverse reactions, although grade 3 events were observed in 4 patients (15.3%), no severe renal toxicity or vomiting was found. S-1 and weekly low-dose cisplatin combination chemotherapy in patients with advanced NSCLC showed an acceptable response rate, overall survival time, and toxicity. Because this regimen can be performed in an outpatient setting, it might be an alternative useful and convenient option. Further investigations with a large population are required to confirm our results.

Clinical Efficacy of Levofloxacin in Elderly Patients with Respiratory Tract Infections

Levofloxacin, the I-isomer of ofloxacin, is presently being investigated for the management of infections caused by a wide range of pathogens, from Gram-positive cocci to Gram-negative bacilli.llJ Levofloxacin possesses the advantages of ofloxacin, such as excellent pharmacokinetic transport to the active site. However, since levofloxacin requires half the ofloxacin dose to achieve equal clinical efficacy, it may also be better tolerated by the patientPl The aim of this study was to evaluate the clinical efficacy of levofloxacin in treating acute respiratory tract infections (RTIs) , either presenting as acute pneumonia or bronchitis, or as a secondary infection in patients with chronic respiratory disease. In addition, the efficacy of levofloxacin in patients with pneumonia caused by unidentified bacteria was also studied. 87 patients were enrolled in the study (38 males and 49 females). Of these, 58 were outpatients, while the remaining 29 were treated in hospital. The mean age (± SD) of the patients was 69.9 (± 16.9; range 20 to 93) years. 37 patients were diagnosed as having pneumonia, including 14 with senile dementia as a complication. Another 21 patients had a secondary infection in addition to their chronic RTI. The remaining 29 patients were treated for an episode of acute bronchitis. The severity of the infection was classified as mild in 40, moderate in 43, and severe in 4. Outpatients received levofloxacin at a dose of 300mg (lOOmg 3 times daily), while inpatients generally received 600 mg/day administered as a 200mg 3-times-daily schedule. Duration of treatment was 3 days for outpatients, and 7 days for hospitalised patients. The overall clinical efficacy of levofloxacin was evaluated on both day 3 and day 7 for inpatients, and on day 3 for the outpatients, on the basis of the following: subjective symptoms, fever, C-reactive protein, and chest x-rays. Clinical efficacy rates in patients with pneumonia were 88.9 and 88.5% when assessed at day 3

Significance of Plasminogen Activators and Plasminogen Activator Inhibitors in Human Lung Cancer

Plasminogen activators (PAs) are serine proteases which convert plasminogen to plasmin and play a major role to regulate intravascular fibrinolysis and extracellular proteolysis.1 At least two types of plasminogen activator, tissue plasminogen activator (t-PA), urokinase (UK), have been identified. UK and its precursor, pro-UK, which are released from cancer cells and bind to specific cell surface receptor of these cells,2–3is considered to play important roles in tumor invasion or metastsis by regulating the degradation of the extracelluler matrix.