Failure of orally administered dipyridamole to enhance the antineoplastic activity of fluorouracil in combination with leucovorin in patients with advanced colorectal cancer: a prospective randomized trial.

PURPOSE: A randomized trial was performed to investigate the ability of the nucleoside transport inhibitor dipyridamole (DP) to enhance the antitumor activity of fluorouracil (5-FU)/leucovorin (folinic acid [FA]). PATIENTS AND METHODS: One hundred eighty-one untreated patients with advanced colorectal cancer were randomized to receive 5-FU 600 mg/m2 plus FA 300 mg/m2 on days 2 to 4 with or without DP 75 mg orally three times daily on days 1 to 5. Cycles were repeated every 3 weeks. Only patients with documented tumor progression before therapy were eligible. 5-FU pharmacokinetics using high-performance liquid chromatography (HPLC) were assessed in 11 nonrandomized patients receiving paired cycles with or without DP. RESULTS: One hundred seventy-four patients were assessable for toxicity and response. There was no significant difference in toxicity, except DP-related headache in 24% of patients. An objective response rate of 15% (one complete response [CR] and 13 partial responses [PRs]) for 5-FU/FA and 13% (two CRs and nine PRs) for 5-FU/FA/DP was observed. The dose-intensity of 5-FU delivered was significantly higher (1.09- to 1.16-fold) for the DP-containing arm. Pharmacokinetic parameters of 5-FU did not differ significantly, except for a prolonged half-life (t1/2) induced by DP. The median time to progression (P = .8) and the median survival time (11.6 months for 5-FU/FA v 9.3 months for 5-FU/FA/DP; P = .14, log-rank test) were not different between treatment arms. CONCLUSION: Orally administered DP did not improve the antineoplastic activity of 5-FU/FA in patients with advanced colorectal cancer when used at this dose and schedule. The observed increase in 5-FU dose-intensity for FU/FA/DP was not clinically relevant.

Recombinant single-chain urokinase-type plasminogen activator during acute myocardial infarction.

Recombinant single-chain urokinase-type plasminogen activator was intravenously administered in 2 different doses in 24 patients with acute myocardial infarction and angiographically proved occlusion of the infarct-related artery. Patients with first infarction without contraindications of thrombolysis were treated within the first 4 hours after the onset of symptoms. Group A (12 patients) received 20 mg of rscu-PA as a bolus followed by 60 mg infused over 1 hour and group B received 10 mg as a bolus and 30 mg as infusion. The 2 groups showed no significant difference in age, sex, height, weight, time between onset of symptoms and start of therapy, peak values and course of infarct-related enzymes. Time to reperfusion was 43 minutes in group A versus 67 minutes in group B (p less than 0.005). The rate of reperfusion 90 minutes after start of treatment was 91% in group A and 50% in group B (p less than 0.001). Plasma levels of fibrinogen, plasminogen and alpha-2-antiplasmin did not differ significantly in both groups. Systemic lytic state (fibrinogen less than 100 mg/dl) occurred in 33% of group A and in 9% of group B. Intravenous infusion of 80 mg (but not 40 mg) of rscu-PA led to reperfusion of the occluded coronary artery in nearly all patients. Approximately one-third of the patients treated with this dose demonstrated systemic lysis.

Molecular weight analysis of proteinuria in experimental glomerulopathies.

The quantity of urinary proteins and their molecular weight composition was analyzed in different experimental glomerulopathies using the SDS-PAA-electrophoresis. Masugi nephritis, heterologous and autologous immune complex nephritis as well as D-penicillamine induced glomerulonephritis were studied in rabbits, guinea pigs and rats. The procedure allows (1) to distinguish physiological from low grade glomerular proteinuria by their respective characteristic patterns in early disease stages (2) to follow up the disease course of individual animals without sacrifice and (3) to discriminate species specificity of physiological urinary proteins. It is recommended to use this technique of urinary protein analysis in experimental conditions, where mild glomerular damage is expected.