Akira Sakuma

A Phase II study of vinorelbine, a new derivative of vinca alkaloid, for previously untreated advanced non-small cell lung cancer

Abstract To evaluate the effectiveness of vinorelbine (NVB) in patients with non-small cell lung cancer (NSCLC), a late Phase II study was conducted. A total of 80 patients with Stage III or IV NSCLC who had no previous therapy were entered into the study. Seventy-nine patients were eligible for response and toxicity. NVB was administered weekly by intravenous injection at a dose of 25 mg/m 2 in 20 ml of saline and was generally administered in four cycles or more, unless patients had disease progression. Of the 79 eligible patients, 23 (29.1%) showed a partial response (95% confidence interval, 19.1–40.4%). The median duration of partial responses was 14.7+ weeks. The median survival time for all patients was 40.1+ weeks. The major toxicity was leukopenia. Grade 3 and 4 leukopenia occurred in 48 patients (60.8%). Other toxicities of grade 3 or more included anemia (6.3%), local cutaneous reaction (3.8%), pneumonitis (1.3%), nausea and vomiting (1.3%), mucositis (1.3%) and constipation (1.3%). The absolute dose-intensity of NVB was 22.33 mg/m 2 /week. A weekly schedule of intravenous administration of 25 mg/m 2 /week of NVB was reasonable for maintenance of activity, and acceptable for toxicity in the chemotherapy of advanced NSCLC.

Double-blind test of human urinary macrophage colony-stimulating factor for allogeneic and syngeneic bone marrow transplantation: effectiveness of treatment and 2-year follow-up for relapse of leukaemia

Summary A randomized, double‐blind placebo‐controlled phase III clinical trial was performed to study the effects of human urinary macrophage colony‐stimulating factor (hM‐CSF) after allogeneic and syngeneic bone marrow transplantation (BMT) in 60 hM‐CSP treated and 59 placebo control patients. HM‐CSF was administered at a daily dose of 2 ± 105 units/kg from day 1 to day 14 after RMT. Significant differences between hM‐CSF and control patients were found in the recovery time to greater than 0. 5 ± 109 granulocytes/1 and the survival rate during the initial 120 d without retransplantation. There was no difference in the incidence or grade of graft‐versus‐host disease (GVHD). There was no difference in the rate of leukaemic relapse at 24–36 months after BMT in patients with acute lymphocytic. acute non‐lymphocytic, or monocytic leukaemia. The results of this trial show that human M‐CSF improves the outcome of BMT without any influence on the occurrence of leukaemic relapse or GVHD.

Clinical effects of MND-19 (Inosiplex) on subacute sclerosing panencephalitis: — A multi-institutional collaborative study—

A total of 151 cases of subacute sclerosing panencephalitis (SSPE), comprising 89 cases treated with MND-19 (Inosiplex) and 62 untreated cases, were retrospectively investigated as to background characteristics, survival rate and clinical course in order to compare the findings in the 2 groups of cases. The survival rate for the cases treated with MND-19 (MND-19-treated group) was significantly higher than that for the untreated cases (control group), which was also true on stratified analysis or on smoothing of the background factors by means of Coxs multiple regression model. Investigation of the clinical course revealed that progression through the disease stages was significantly slow in the MND-19-treated group, compared with in the control group. Global rating of the clinical course showed that a prolonged remission was obtained in more MND-19-treated cases than control cases. The measles virus antibody titer was in no way affected in the former group. Side effects of MND-19 were observed in 17 of the 89 treated cases (19.1%).

Clinical pharmacologic evaluation of the antiatherosclerotic agent, pyridinolcarbamate. A double-blind crossover trial in the treatment of atherosclerosis obliterans

The antiatherosclerotic effect of pyridinolcarbamate in man has been subjected to the present controlled clinical trial in 43 patients suffering from atherosclerosis obliterans with relatively stable signs and short claudication times (101 ± 8 sec.). To isolate individual factors such as age, sex, constitution, social condition, and spontaneous fluctuations of symptoms from the drug effect, a double-blind crossover technique (within-subject comparison) has been applied. After the initial 3 weeks of placebo wash out, a 10 week regimen of placebo or pyridinolcarbamate (1.5 Gm. daily) and another 10 weeks of alternative regimens were given successively. After drug regimen the prolonged crest time in plethysmography was shortened (p < 0.01) and claudication time prolonged with a statistically significant correlation (p < 0.05). The statistically significant preference for pyridinolcarbamate over placebo has been established by the effect on crest time alone, claudication time alone, and also major symptoms including ischemic ulcer, cyanosis, pain, and paresthesia of affected legs (p < 0.001). The relatively slow-acting and persistent effect of pyridinolcarbamate on the clinical signs observed in these patients encourages further histologic analysis of its effect on atheromatous lesions in man.

Acceleration of DNA synthesis in post-hepatectomized regenerating liver of normal rat by insulin and glucagon

Abstract The effect of insulin and/or glucagon on the cumulative incorporation of tritiated thymidine was studied using normal rats with post-hepatectomized regenerating livers. Although the cumulative incorporation value was low at 20 hr and increased thereafter, a significant difference was not found between control and treated rats up to 60 hr after the operation. However, when rats were distributed according to the time the incorporation reached a maximum, there was a significant difference in the distributions between control rats and rats treated with combined insulin and glucagon (P=0.0303); more rats showed maximum incorporation at earlier times after treatment. These results suggest that a combination of the two hormones accelerates DNA synthesis in post-hepatectomized regenerating liver of normal rats.

A placebo-controlled double-blind study of epalrestat (ONO-2235) in patients with diabetic neuropathy

‘Department of lnternal Medicine, Tohoku Kosei-Nenkin Hospital bThe Third Department of Internal Medicine and ‘The Neurological Department of lnternal Medicine, Nagoya University School of Medicine dThe Third Department of lnternal Medicine, Shiga University of Medical Science, Faculty of Medicine ‘The Third Department of lnternal Medicine, Hiroshima University School of Medicine ‘Department of Internal Medicine, Tokyo Saiseikai Central Hospital Qeparfment of Ciinical Pharmacology, Medical Research Institute, Tokyo Medical & Dental University School of Medicine, lapan

Evaluation of the Effect of CDP-Choline on Poststroke Hemiplegia Employing a Double-Blind Controlled Trial: Assessed by a New Rating Scale for Recovery in Hemiplegia

A double-blind study was conducted in order to evaluate the effect of CDP-choline on functional recovery of hemiplegia. A standardized 12-grade scale (Hemiplegia Function Test) was utilized for the evaluation. The results indicate that for the upper limbs, doses of 1,000 and 250 mg of CDP-choline were superior to placebo at 8 weeks. The higher dose showed an effect at 4 weeks equal to that at 8 weeks while the effect of the lower dose was slower but reached the same level of effect as the higher dose at 8 weeks. Similar results were obtained for the lower limbs but the effectiveness was not statistically significant. The lesser effect for the lower limbs could be attributed to the relatively small number of patients in the early stages of recovery in the present series. No significant differences were found for the effects on subjective symptoms, neurological signs and overall judgment of the physicians. The findings suggest that CDP-choline promotes natural recovery in hemiplegia.

Comparison of Efficacy of Amoxapine and Imipramine in a Multi-Clinic Double-Blind Study Using the WHO Schedule for a Standard Assessment of Patients with Depressive Disorders

A multi-clinic double-blind controlled study on amoxapine in comparison with imipramine, using the WHO Schedule for a Standard Assessment of Patients with Depressive Disorders, was performed and the data were analyzed with 111 patients. The assessment of severity of illness and overall improvement indicated clearly the superiority of the antidepressive effect of amoxapine to that of imipramine. The onset of antidepressive effect of amoxapine was clearly more rapid than that of imipramine, and in more than half of the patients in the amoxapine group the improvement was seen within four days following the drug administration, Amoxapine was superior to imipramine in terms of safety and usefulness. The side-effects due to amoxapine appeared less frequently and were less serious than with imipramine. The difference between amoxapine and imipramine was especially remarkable for hypotensive effect. The antidepressive effect of amoxapine was superior to that of imipramine for almost all symptoms and signs. Amoxapine displayed an especially remarkable effect on psychomotor retardation, depressive feeling, anxiety and tension, somatic complaints and sleep disturbance.

A multi-centre double-blind controlled trial of glucagon and insulin therapy for severe acute hepatitis.

SummaryA cooperative study was conducted to determine the efficacy of one week of treatment with infusion of 1 mg glucagon and 10 units insulin twice daily in severe acute hepatitis. Ninty-eight patients with either prothrombin time less than 60% or thrombotest or hepaplastin test less than 50% of normal were randomly assigned to hormone or placebo treatment. SGOT and SGPT values dropped after treatment with a gradual decrease or increase in total serum bilirubin or cholesterol levels similarly in both groups receiving hormone or placebo. Deranged prothrombin time improved more rapidly in the hormone group than in the placebo group. Glucagon and insulin infusion may stimulate recovery of the liver from injury.

Effects of enoximone on exercise tolerance in patients with mild to moderate heart failure

To evaluate the efficacy of enoximone on exercise tolerance in patients with mild to moderate heart failure, 33 patients underwent cardiopulmonary exercise tests before and 3 hours after placebo or after receiving 25 or 100 mg of enoximone administered randomly in a double-blind manner. The electrocardiogram was monitored and blood pressure measured every minute throughout cycle ergometer exercise testing with a ramp protocol in which the work rate increased 1 W every 6 seconds after a 4-minute 20-W warm-up. Minute ventilation, oxygen uptake (VO2), and carbon dioxide output were measured every 10 seconds in order to determine anaerobic threshold (AT) and peak VO2. Five patients were excluded from evaluation before breaking the double-blind key because of insufficient data. Heart rate increased and systolic blood pressure decreased throughout the testing only in the group taking 100 mg (n = 10). Significant increases in AT (14.4 to 16.2 ml/min/kg) and peak VO2 (20.8 to 22.9 ml/min/kg) were observed in the group taking 100 mg. The increases in AT showed a dose response, namely +0.7% in the placebo (n = 9), +6.9% in the 25-mg (n = 9) and 12.5% in the 100-mg group. The work rates at the AT point increased in the 25- and 100-mg groups. These results indicate that a single oral administration of enoximone improves exercise tolerance in patients with mild to moderate heart failure.