Doxorubicin in combination with verapamil in advanced colorectal cancer. A phase II trial.

The possibility that verapamil might increase the sensibility of colorectal carcinomas to doxorubicin was studied in 24 patients without previous cytotoxic chemotherapy. The treatment started with oral verapamil, which was escalated up to the individual maximum tolerable dose (defined by prolongation of P-Q in ECG, fall in blood pressure, or dizziness). The median maximum tolerable dose was 600 mg (range 320-1,440 mg). During continued verapamil administration the patients then got weekly infusions of doxorubicin, 25 mg/m2. The median number of doxorubicin courses was 8 (range 2-22). Among 21 patients evaluable for response and toxicity two partial remissions occurred but no complete remission. The study did not indicate enhanced cardiac, hematological or non-hematological toxicity from the combined treatment.

Levomepromazine (Nozinan) reduces nonspecific bronchial hyperreactivity in asthmatics.

Ten patients with bronchial asthma were challenged with histamine before and after receiving saline and active drug (levomepromazine or antazoline) (a total of six challenges). The antihistaminic effect of levomepromazine (25 mg) was found to be comparable to that of antazoline (100 mg), evaluated from skin prick tests. Prechallenge forced expiratory volume in one second (FEV1) was found to be larger after levomepromazine than after antazoline (p less than 0.05), indicating a direct bronchodilating effect. This increased threshold airway calibre may have influenced the results of challenge, but change in provocative concentration producing 20% fall (PC20) was not statistically significantly correlated to change in FEV1. Levomepromazine increased PC20 2-doubling concentration compared to antazoline (p less than 0.05). Variation was observed in two minutes' ventilation during tidal volume breathing challenge. However, there was no statistically significant variation in two minutes' ventilation during challenge after receiving levomepromazine or antazoline. It was concluded that levomepromazine possesses a bronchodilating capacity and reduces bronchial hyperreactivity.

[Effect of posture on the diuretic treatment of decompensated cirrhosis and heart failure]. / Betydningen af kroppens stilling for det diuretiske respons ved behandling af dekompenseret cirrose og morbus cordis.

The diuretic effect of the supine position was evaluated in six patients with cirrhosis and ascites and six with congestive cardiac failure. All patients received 1 mg bumethanide intravenously and were randomly assigned to either bed rest in the supine position or normal daily activity in the upright position for the next six hours. The diuretic response was similar in patients with heart failure and cirrhosis, and was significantly greater in the supine than in the upright position: mean 1,133 v 626 ml/6 h (p less than 0.01). The natriuresis was similarly greater during recumbency: mean sodium 96 v 45 mmol (mEq)/6 h (p less than 0.01), and the excreted potassium in six hours was similar in both postures. The glomerular filtration rate was 100 and 66 ml/min (p less than 0.01) and the heart rate 76 and 83 beats/min (p less than 0.05) in the supine and upright positions, respectively. Plasma concentrations of noradrenaline, renin, and aldosterone rose significantly during the upright position. The results suggest that the attenuated response to intravenous bumethanide in the upright position and during normal daily activity may be due to the activation of several, homoeostatic mechanisms which may reduce the excretion of water and salt.

Intramuscular betamethasone dipropionate vs. oral prednisolone in hay fever patients.

In a double-blind group comparative study, 36 adult, birch pollen-allergic outpatients with seasonal rhinoconjunctivitis, were treated with either oral prednisolone 7.5 mg daily for 3 weeks or an injection with 2 ml suspension of betamethasone dipropionate and betamethasone disodium phosphate (Diprospan) immediately prior to the birch pollen season. Both treatments were able to prevent an increase in symptoms from the nose and the eyes during the 3-week birch pollen season. There was no significant difference in symptom score or nasal peak flow between the two treatments. However, there was a significant suppression of adrenal gland function after oral prednisolone treatment in contrast to Diprospan treatment. Unless there are contraindications for treatment with depot steroid injections (children, pregnant women, patients suffering from peptic ulcer, tuberculosis, eye disease, herpes, hypertension or diabetes) it seems to be a reasonable alternative to oral prednisolone in hay fever patients.

Diuretic treatment in decompensated cirrhosis and congestive heart failure: effect of posture.

The diuretic effect of the supine position was evaluated in six patients with cirrhosis and ascites and six with congestive cardiac failure. After fasting overnight in bed the patients received bumetanide 1 mg intravenously and were then immediately randomly assigned to either bed rest in the supine position or normal daily activity in the upright position for the next six hours. Two days later the procedure was repeated, the patients being assigned to the other posture. The diuretic response was similar in patients with heart failure and cirrhosis, and was significantly greater in the supine than in the upright position: mean 1133 v 626 ml/6 h (p less than 0.01). The natriuresis was similarly larger during recumbency: mean sodium 96 v 45 mmol(mEq)/6h (p less than 0.01), and the excreted potassium in six hours was similar in both postures. The glomerular filtration rate was 100 and 66 ml/min (p less than 0.01) and heart rate 76 and 83 beats/min (p less than 0.01) in the supine and upright positions respectively. Plasma concentrations of noradrenaline, renin, and aldosterone were all raised even when the patient adopted the supine position, and a further significant rise was observed during the upright position. The results suggest that the attenuated response to intravenous bumetanide in the upright position and during normal daily activity may be due to the activation of several homeostatic mechanisms that may reduce the excretion of water and salt.

Efficacy of and errors in randomized multicenter trials. A review of 230 clinical trials.

An attempt was made to study the efficacy in and one of the errors of randomized multicenter clinical trials. Efficacy was defined for the present purpose as a statistically significant clinical difference between at least 2 of the treatment arms studied. The error studied was defined here as non-excluded protocol deviations found during a systematic record review. The nature (multicenter randomized trial or un-controlled pilot study) of 8 so-called "breakthrough" studies which seemed particularly important for future cancer treatment was also established. The number of yearly randomized trials seems to have increased by a factor of 10 between 1969 and 1981, as judged by the abstracts published by the American Society of Clinical Oncology. 23% yielded statistically significant results, which is 18% over the 5% expected chance significances. Of 174 papers and abstracts published by one group, only 18 were reviewable original studies. The corresponding figures for another group was 6 of 22. This explains why only 8 scientifically new statistical significances were found in one series of 76 original articles. The mean dose of cytostatics actually given to 192 breast cancer patients varied, as judged by a record review, between 71 and 93% of the protocol doses. These figures agree with the 15-30% of nonexcluded protocol deviations found previously. Of the 8 "breakthrough" studies, 7 were single center pilot studies without randomized controls, and only 1 was a randomized multicenter study. It is suggested that more relevant questions can be asked in multicenter randomized clinical trials if they are based on promising single center pilot results, and that record reviews should be performed so that protocol deviations can regularly be reported.