Efficacy of the combination of nilutamide plus orchidectomy in patients with metastatic prostatic cancer. A meta-analysis of seven randomized double-blind trials (1056 patients).

OBJECTIVE: To review the efficacy of the combination of the anti-androgen nilutamide (Anandron) plus orchidectomy in patients with stage D prostate cancer who had received no previous treatment. PATIENTS AND METHODS: The results of seven randomized double-blind trials were analysed. In these studies patients were followed up until progression of disease or withdrawal for other reasons. Bone pain, urinary symptoms, performance status, levels of prostatic acid phosphatase (PAP) and alkaline phosphatase (AP) were evaluated before treatment and after 1, 3, 6, 12 and 18 months of treatment. Bone scans and X-rays were taken every 6 months. The best objective response, the time of progression and the time of death were recorded. The changes from baseline in symptoms and levels of tumour markers at month six and the percentages of objective regressions in the two treatment groups were compared using the Cochran-Mantel-Haenszel test stratified by study. Peto's method was used for the analysis of time to progression and of survival. RESULTS: Of the 1191 patients enrolled in all the original trials, 1056 were eligible. In the group of patients treated with nilutamide 50% had complete or partial regression of disease compared with 33% of those who were given a placebo (P < 0.001); bone pain and levels of PAP and AP were improved or returned to normal significantly more frequently (P < 0.01); the odds of disease progression were significantly reduced (odds ratio 0.84, P = 0.05); the odds of death from cancer and from other causes were reduced but the difference was not statistically significant. CONCLUSIONS: The combination of nilutamide and orchidectomy has a beneficial effect on pain of metastatic origin, levels of tumour markers, the objective response of disease and the time to disease progression. This treatment combination might also improve survival.

Study of the potential reversal of triazolam memory and cognitive deficits by RU 41 656 in healthy subjects.

The potential antagonism of a single oral dose of RU 41 656 (10 mg) on the memory and attention disturbances induced by oral administration of triazolam (0.25 mg) have been investigated in a 3-period, placebo controlled, double blind, cross-over study involving 12 healthy young volunteers. The effects of the compounds were evaluated by objective tests (Buschke selective reminding test, CFF, simple reaction time, tapping, arithmetical calculation) and subjective measurements (visual analogue scale, side effects questionnaire). Measurements were taken before treatment and 2, 4 and 7 h after RU 41 656 intake. Triazolam caused anterograde amnesia as already described with other benzodiazepine with few sedative effects at this dosage. Under the experimental conditions of the trial, RU 41 656 failed to counteract the memory deficits induced by triazolam.

RU 41,656 does not reverse the scopolamine-induced cognitive deficit in healthy volunteers.

The potential antagonism of a single oral dose of RU 41,656 10 mg on the memory and attention disturbances induced by scopolamine 0.6 mg s.c. have been investigated in a 3 period, placebo controlled, double blind, cross over study in 12 healthy, young volunteers. The effects of the compounds were evaluated by objective tests (Buschke selective reminding test, CFF, simple reaction time, tapping, arithmetical calculation) and subjective measurements (visual analogue scale, side effects questionnaire). Measurements were taken before treatment and 2, 4 and 7 h after RU 41,656. Scopolamine caused anterograde amnesia and sedative effects as which were not counteracted by RU 41,656.

Peripheral antiglucocorticoid action of RU 486 in man.

In order to evaluate the peripheral antiglucocorticoid activity of RU 486 in man we examined its ability to antagonize the effects of acutely administered glucocorticoids on blood leukocyte counts. The study was performed on eight normal male subjects. They were given 400 mg RU 486 (or placebo) orally at 0730 h and 1 mg dexamethasone (or placebo) orally at 0830 h, using a double-blind, cross-over, latin-square design with a one week interval between each of the four different treatments. Circulating eosinophils, lymphocytes, and neutrophils were counted at 0730 h and 1330 h, and their variations (1330 h counts/0730 h counts x 100) were compared under each treatment. For each cell type, dexamethasone induced variations (eosinophil and lymphocyte drop, neutrophil rise) which were significantly (P less than 0.05) different from those under the three other treatments; these latter treatments (placebo, RU 486, and RU 486 + dexamethasone) were equivalent to each other, inducing no variations of leucocyte counts. These data show that RU 486 inhibits dexamethasone induced leukocyte changes; this simple test provides a useful means to further analyse the peripheral antiglucocorticoid activity of RU 486 in man.

Acute effects of amitriptyline on human performance and interactions with diazepam.

The effects of psychomotor performance and attention of amitriptyline 75 mg administered without and with diazepam 10 mg have been investigated in 12 healthy subjects. The effects of the compounds were evaluated by objective tests (measurement of body sway, critical flicker fusion, visual reaction time, tachistoscopy, short term visual memory, tapping test, arithmetical calculation and Clement's code) and subjective measurements (visual analogue scales and side effects questionnaire). Measurements were taken before treatment and after 1, 3, 6, 8 and 24 h. Placebo did not affect either the objective or the subjective measurements. Diazepam caused a reduction in attention and performance after 1 h which had disappeared at 3 h. Amitriptyline caused a marked reduction in attention and performance, reaching a peak 3 hours after drug administration and persisting until 8 h. the deterioration in vigilance induced by amitriptyline was potentiated by concomitant diazepam.

Effects of single oral doses of clobazam, diazepam and lorazepam on performance tasks and memory.

The effects on memory and psychomotor performance and the subjective effects of three anxiolytic benzodiazepines (lorazepam 2 mg, diazepam 10 mg and clobazam 20 mg p.o.) have been evaluated in a double-blind, placebo-controlled, cross-over study in 10 healthy volunteers. At each session, measurements were made prior to and +3.5 h after drug administration, except in the case of REY's test, which was presented at H + 1 h (learning) and was evaluated at H + 8 h and at H + 24 h (delayed recall). Single clinical doses of diazepam and lorazepam caused anterograde amnesia by disturbing acquisition, consolidation and retrieval. Clobazam did not impair memory. Lorazepam impaired performances in all the tests used to evaluate perception, immediate memory, reaction time, psychomotor skill and intellectual capacity. Diazepam caused a decrease in cortical arousal and the speed of perception of visual stimuli, whereas clobazam increased reaction time and reduced cortical arousal. Lorazepam caused a significant degradation of performance relative to the other two treatments.

Pharmacological and clinical studies of the antiandrogen Anandron.

This paper summarizes the animal and human studies with Anandron available at the time of the meeting. The following was demonstrated in the rat and confirmed in man: interaction of Anandron with the prostatic androgen receptor, antiandrogen activity against testosterone (in particular against the early transient rise induced by LHRH analogs) and adrenal androgens. Thus, as shown in 4 different double blind studies performed in stage D2 prostrate cancer patients, the combination of Anandron with surgical or chemical castration enhanced the beneficial effects of castration alone and thus seems a step forward in the hormonal treatment of prostatic carcinoma.

Prognostic value of lymphograms in chronic lymphatic leukemia.

Chronic lymphatic leukemia (CLL) is a disease with a prognosis that has previously been difficult to assess. In recent years, this problem has largely been overcome by various classifications based on clinical and hematologic findings. This article presents the results of a study designed to show the value of lymphograms in assessing the prognosis. These results show that prognosis is associated with lymph node structure, as assessed by lymphography. Lymphography, as an investigation is superior to scanning or echography, since these give information merely on nodal size. It is proposed that lymphograms should be used for assessing the gravity of the disease and help in the choice of therapy.

[Blood pressure in the child and the adolescent. Effect of age, sex, height, weight and heart rate]. / Les pressions artérielles de l'enfant et de l'adolescent. Influence du sexe, de l'âge, de la taille, du poids et de la fréquence cardiaque.

6,391 school children in the department of Seine-Saint-Denis were studied to determine the normal limits of blood pressure, its variations with age and sex, and its correlations with height, weight and heart rate. Blood pressure has a nearly perfect Gaussian distribution. Average blood pressures increase linearly with age according to sex. Boys have higher systolic blood pressures after the age of 14 and higher diastolic blood pressures after the age of 16. The estimated incidence of hypertension was 3,1% systolic hypertension and 2.2% diastolic hypertension. There was a very close relationship between systolic and diastolic blood pressure. Average systolic and diastolic blood pressures increased very significantly with height and weight, in both sex. Heart rate decreased with age. The average blood pressure was not related to heart rate. Blood pressure charts, related to age, sex, height and weight, allow follow-up of arterial blood pressure as children grow up and may lead to a better understanding of the mechanism of hypertension.

[Mortality due to carcinoma of the stomach between 1954 and 1974. Changes in France (author's transl)]. / Mortalité par cancer de l'estomac de 1954 à 1974. Evolution en France.

A study of changes in mortality due to carcinoma of the stomach in France between 1954 and 1974 was undertaken on the basis of probable levels standardised on the French population in 1968. There was a marked fall in this mortality for both sexes. In the male, the initial level in 1954 was 54.8/100 000 and the decrease was of the order of 1.35 deaths per 100 000 per year, i.e. an annual fall of -3.21%. This phenomenon was more marked during the second period (1965--1974): - 3.88%, than during the first period (1954--1963: - 2.38%. In the female, with an initial mortality rate of 31.25/100 000, the annual decrease was 31.25/100 000, i.e. an annual fall of - 3.49%. This fall was - 3.09% for the first ten year period and - 4.80% for the second period. Thus in France, in common with many other countries, there has been a marked decrease in mortality due to carcinoma of the stomach, for both sexes, and this phenomenon became progressively more notable during the period of the study.

[Mortality of carcinoma of uterine cervix in France : 1950-1976, trends and geography (author's transl)]. / Mortalité par cancer du col de l'utérus en France, de 1950 à 1976. Etude de la tendance et répartition géographique.

A study of changes in mortality due to carcinomas of cervix uteri in France between 1950 and 1976 was undertaken. Rates increased slightly over the whole period (0.44% per year). However, from 1950 to 1968 there was an increase (1.9% per year) and from 1969 to 1976 a decrease (1.17%). This decrease may be due partly to improvements in diagnosis, screening and cure. The geographical distribution has not shown any regional particularity. There is a high significant correlation with geographical distribution of breast cancer mortality, a hitherto unknown finding in France.

[Mortality of bladder cancer in France: 1952--1976. Trends and increase, particularly in the South of France (author's transl)]. / Mortalité par cancer de la vessie en France, de 1952 à 1976. Son évolution croissante et sa répartition géographique particulière dans le sud de la France.

Trends in mortality from bladder cancer have been described with several statistical methods using bi and multivariate analysis. Between 1952 and 1976, the mortality by bladder cancer was marked by an increase for both sexes with a predominance among the males (annual increase + 3,65%, against 1.34% among the females). In 1976, the age-adjusted rate/100,000 of mortality was 11,35 for males and 3,20 for the females showing an high sex-ratio. The computerized mapping of this cancer geographical distribution shows a significant predominance in the south of France and also a high statistically significant correlation with the geographical distribution of lung and gallbladder cancer mortality in France.

[Relations between biomedical variables: mathematical analysis or linear algebra?]. / Les relations entre variables biomédicales: Analyse mathématique ou algèbre linéaire?

The authors, after a short reminder of one pattern's structure, stress on the possible double approach of relations uniting the variables of this pattern: use of fonctions, what is within the mathematical analysis sphere, use of linear algebra profiting by matricial calculation's development and automatiosation. They precise the respective interests on these methods, their bounds and the imperatives for utilization, according to the kind of variables, of data, and the objective for work, understanding phenomenons or helping towards decision.

[Use of models in the study of survival in oncology]. / Utilisation de modèles dans l'étude de la survie en carcinologie.

Observation of numerous survical surves connecting the survival rates with time usually expressed in yearly intervals has permited the elaboration of patterns describing survival probability in terms of time. Gross survival patterns, from which the most utilized is the exponential pattern, must be distinguished from comparative surival patterns that debouch into the recovery probleme. Their interest is to caracterize survival for a group of patients with the assistance of a limited number of values (three at most). From that, follow their practical applications: comparison between several groups that may differ either from the characteristics of the discase or from the received treatments and from the vital future forecasting, either on one group's level, or for an individual.

[Is there any bimodality of the age distribution of male mammary cancer (author's transl)?]. / La distribution de l'âge des cancers du sein chez l'homme est-elle bimodale?

The authors study the pattern of the curve concerning breast cancer incidence in males as a function of age. The demonstration is made that such a curve is bimodal and, more precisely, could be satisfactorily considered as being made up of the juxtaposition of two normal distribution curves. The interval thus individualized between the mean age of both groups is remarkably steady between 17 and 20 yrs. The phenomenon is not blurred by regrouping the data and the patients population could be divided into two subgroups: one with a mean age of 147 yrs, with a standard deviation of 9 yrs, and bearing on 246 patients, the other one including 1.100 patients averaging 66.5 yrs old with a standard deviation of 9.9 yrs.