Effect of androgen deprivation therapy on local symptoms and tumour progression in men with metastatic carcinoma of the prostate.

OBJECTIVE: To evaluate and compare the effects of medical or surgical castration combined with either nilutamide (Anandron) or placebo on symptoms of local tumour progression in men with carcinoma of the prostate. METHODS: The results from twin, randomised, prospective, placebo-controlled trials were analysed. 434 patients received nilutamide 300 mg/day for 1 month and 150 mg thereafter, and 434 received a matched placebo from either the day of orchidectomy or the first leuprolide injection. Before treatment, and at months 1, 3, 6 and every 6 months thereafter, urinary obstruction and tumour volume were evaluated. Data on adverse or intercurrent events affecting the urological system were documented. RESULTS: Before treatment, urinary obstructive symptoms and tumour volume were similar in both treatment groups. After treatment, improvement in urinary obstructive symptoms accompanied a decrease in prostate volume. The majority of men in both treatment groups reported an improvement in obstructive voiding symptoms. However, total adverse events secondary to local symptoms were significantly less frequent in the nilutamide-treated patients (20%) compared with the placebo-treated patients (35%). Only a small percentage of men in both treatment groups had disabling local symptoms and only 2% experienced problems with incontinence. CONCLUSIONS: Local symptoms from primary tumour growth are relatively common in patients with metastatic carcinoma of the prostate and are favourably influenced by hormonal therapy. In these trials, the problems resulting from local tumour progression were significantly fewer in the group treated with castration plus nilutamide compared with the group treated with castration plus placebo.

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.

[Acadione, a new long-term treatment of rheumatoid polyarthritis]. / L'acadione, un nouveau traitement de fond de la polyarthrite rhumatoïde.

This article summarizes the authors' experience and data from the literature regarding acadione, a medication like D-penicillamine with a thiol radical, in the treatment of rheumatoid arthritis. Two control studies versus placebo and two control trial versus D-penicillamine prove the effectiveness of the treatment and demonstrate a similar activity between 1 g of acadione and 600 mg of D-penicillamine. The side-effects of acadione are similar of those of D-penicillamine, essentially rash, toxic dermatitis, agueusia, proteinuria, which disappear upon discontinuation of the treatment. The fact that the patient exhibited a side effect with D-penicillamine, increases, the risk with acadione, but this is not systematic, which is the main advantage of this product.

[Tiopronine and rheumatoid polyarthritis]. / Tiopronine et polyarthrite rhumatoïde.

This article summarises the authors' experience and the data of the literature concerning Tiopronine, a drug with a thiol function like D-penicillamine, in the treatment of rheumatoid arthritis. Two controlled trials versus placebo and two controlled trials versus D-penicillamine demonstrated the effectiveness of treatment and the identical action of 1 g of Tiopronine and 600 mg of D-penicillamine. The side effects of Tiopronine are very similar to those of D-penicillamine: essentially rash, toxiderma, aguestia, proteinuria, which resolve when treatment is stopped. Patients with a past history of side effects with D-penicillamine have an increased risk of developing side effects with Tiopronine, but this risk is not systematic, which constitutes the principal value of this drug.

[Treatment of systemic scleroderma with factor XIII in 86 patients, with long-term follow-up]. / Traitement de la sclérodermie systémique par le facteur XIII chez 86 malades suivis à long terme.

Eighty-six patients with progressive systemic sclerosis were given coagulation factor XIII intravenously in different dosage regimens. The mean duration of treatment was 19 +/- 18 months and patients were followed up for 22.9 +/- 18.8 months. Improvement or stabilization of the lesions was obtained in 44/86 patients and exclusively concerned skin lesions; there was no improvement in visceral lesions. The drug was well tolerated in short-and long-term treatment. It is concluded that factor XIII demonstrated lasting effectiveness in one-half of the patients treated.

Treatment of progressive systemic sclerosis using factor XIII.

A double-blind, randomized crossover trial was carried out in 25 patients with progressive systemic sclerosis to compare the effectiveness and tolerability of treatment with Factor XIII with that of placebo. Patients received twice daily intravenous injections of either Factor XIII or placebo for 3 weeks and, after a wash-out period of 6 weeks, were crossed over to the alternative medication for a further 3 weeks. Assessments made by the physician and patients at the end of each treatment period indicated that Factor XIII was significantly better than placebo in improving the cutaneous manifestations of the disease and these opinions were supported by the significant improvement in the function index which was used to assess the degree of motor disability. Both local and general tolerability of Factor XIII treatment was good and there were no adverse reports.

Type IV hyperlipoproteinemia in patients with algodystrophy.

The present work studies lipid metabolism in patients with algodystrophy (AD). A correct positive correlation (r = 0.75) between the triglyceride levels and low density lipoprotein (LDL)/very low density lipoprotein (VLDL) ratio and the VLDL increase observed by gel disk electrophoresis confirm that a type IV hyperlipoproteinemia is associated with AD. In contrast, the degree of high density lipoprotein (HDL) saturation in cholesterol (HDL-cholesterol/HDL-phospholipids) and the classical atherogenous index (cholesterol/HDL-cholesterol) were not modified. The decrease of plasma post-heparin lipolytic activities (PHLA) was not significant but further studies should be performed to correlate PHLA with a reduced activity of the adipose tissue lipoprotein lipase.

[Algodystrophy and metabolic abnormalities]. / Algodystrophie et anomalies métaboliques.

The French Society of Rheumatology national study of reflex dystrophy revealed a serum glucose greater than 1.20 g/l in 9.09 p. cent of cases, a serum uric acid greater than 70 mg/l in 25 p. cent of men and greater than 60 mg/l in 14 p. cent of women. Serum cholesterol was normal in males, but higher than the mean + 2 sigma in 23 p. cent of females. Serum triglycerides were higher than m + 2 sigma in 55 p. cent of men and 56 p. cent of women. From a group of 80 patients, 54 (67.5 p. cent) had at least one of the three metabolic abnormalities and 49 (61.25 p. cent) were hypertriglyceridaemic. This hypertriglyceridaemia is the most frequent abnormality found. When hyperglycaemia or hyperuricaemia are present it is almost always in association with hypertriglyceridaemia. Hypertriglyceridaemia is more common in algoneurodystrophy of the lower limbs (54/78, 69 p. cent) than in algoneurodystrophy of the upper limbs (5/22, 22.7 p. cent). Algoneurodystrophy is more often primary, when it occurs in the lower limbs and post-traumatic when it occurs in the upper limbs. A prospective study comparing several parameters of lipid metabolism in 24 patients with algoneurodystrophy and 15 matched controls showed a significant drop in the HDL Chol/HDL P1 ratio and in the DHL - HDL Chol/TG ratio in patients with algoneurodystrophy. Serum insulin was comparable in the 2 groups. Lecithin cholesterol acyl transferase (LCAT), SGOT, SGPT and GGT were normal. The essential role of hypertriglyceridaemia in the genesis of the characteristic bony lesions of algoneurodystrophy is discussed.

[Algodystrophy and metabolic anomalies]. / Algodystrophie et anomalies métaboliques.

The French Society of Rheumatology national study of reflex dystrophy revealed a serum glucose greater than 1.20 g/l in 9.09 p. cent of case, a serum uric acid greater than 70 mg/l in 25 p. cent of men and greater than 60 mg/l in 14 p. cent of women. Serum cholesterol was normal in male cases, but higher than the mean + 2 sigma in 23 p. cent of female cases. Serum triglycerides was higher than m + 2 sigma in 55 p. cent of men and 56 p. cent of women. From a group of 80 patients, 54 (67.5 p. cent) had at least one of the three metabolic abnormalities and 49 (61.25 p. cent) were hypertriglyceridaemic. This hypertriglyceridaemia is the most frequent abnormality found. When hyperglycaemia or hyperuricaemia are present it is almost always in association with hypertriglyceridaemia. Hypertriglyceridaemia is more common in algoneurodystrophy of the lower limbs (54/78, 69 p. cent) than in algoneurodystrophy of the upper limbs (5/22, 22.7 p. cent). Algoneurodystrophy is more often primary, when it occurs in the lower limbs and post-traumatic when it occurs in the upper limbs. A prospective study comparing several parameters of lipid metabolism between 24 patients with algoneurodystrophy and 15 matched controls showed a significant drop in the HDL Chol/HDL P1 ratio and in the DHL--HDL Chol/TG ratio in patients with algoneurodystrophy. Serum insulin was comparable in the 2 groups. Lecithin cholesterol acyl transferase (LCAT), SGOT, SGPT and GGT were normal. The essential role of hypertriglyceridaemia in the genesis of the characteristic bony lesions of algoneurodystrophy is discussed.

Tiopronin (N-[2-mercaptopropionyl] glycin) in rheumatoid arthritis.

Two controlled trials have demonstrated that tiopronin, a new sulfhydryl compound, is active as a slow-acting antirheumatic drug in rheumatoid arthritis. One trial compared 10 patients receiving placebos and 20 receiving tiopronin, 1 gm/day; the second compared two groups of 16 patients who received either placebos or tiopronin, 1.5 gm/day. In addition, 80 patients (56 from the 2 trials plus 24 other patients) were followed up for a long period. Dropout rate for intolerance or inefficacy was comparable to that fund with D-penicillamine. Secondary toxic reactions resembled those of other sulfhydryl compounds.

[Role of pregnancy and related conditions on experimental arthritis of the rat (author's transl)]. / Effet de la gestation et d'états apparentés sur la polyarthrite expérimentale du rat type Pearson.

Pregnancy in Rat induces, as in humans suffering from rheumatoid arthritis, a striking improvement of adjuvant arthritis. This improvement is not associated with an enhancement of corticosteronemia; it does not appear either in pseudo-pregnancy, or in experimental deciduoma. It could rather be related to an immune mechanism; an enhancement of T suppressor lymphocytes associated to a decrease of T helper lymphocyte activity in peripheral blood as suggested by a high response to ConA and low response PHA and PWM during arthritis plus pregnancy. The influence of hormonal factors on recirculation and/or activity of peripheral lymphocytes is not excluded.

Adjuvant arthritis in rat during pregnancy and lactation.

We have studied, in the female rat, the influence of pregnancy, lactation and pseudo-pregnancy on adjuvant arthritis. Pregnancy has a suppressive effect on the arthritis all the more marked as arthritis onset occurs during the third part of pregnancy. Pseudo-pregnancy with or without decidualization of the uterus does not modify the arthritis course; thus the corpus luteum and the decidual tissue cannot account for the observed improvement. Lactation has a beneficial effect that lasts until weaning. Amount of estradiol which insured approximate serum level of pregnant rats improves the polyarthritis. In the same conditions, progesterone remains inactive. Suppression by estradiol is observed in ovariectomized and intact females. Thus, in the female rat, pregnancy, lactation and physiological doses of estradiol improve adjuvant arthritis.

Effectiveness of levamisole in rheumatoid arthritis: Immune changes and long-term results.

After a double-blind trial of 4 months, 40 patients with RA were treated with 100 mg Levamisole. Clinical results were good or excellent in 50%. The immunological status is not a valuable criterion for the selection of patients apt to respond to Levamisole. A good correlation was found between clinical improvement, reduction of ESR, percentage of immunoblasts, rheumatoid factor titre and the enhancement of lymphoblastic response to polyclonal mitogens. The treatment maintenance rate for efficacy was much lower for Levamisole than for D-penicillamine.

[Immunomodulating action of 2-methoxyethanol and homologous derivatives in rats]. / Action immunomodulatrice du méthoxy-2 éthanol et de dérivés homologues chez le rat.

The authors have measured the effects of methoxy-2 ethanol and derivatives or analogs on adjuvant arthritis in Rat, and the activity of methoxy-2 ethanol on humoral responsiveness to antigenic stimuli in Rat. Only methoxy-2 ethanol,1,2-dimethoxyethane and 1-methoxy 2 ethoxy ethane out of 13 tested derivatives, have an inhibitory activity on adjuvant arthritis. Methoxy-2 ethanol induces a significant depression of antibody production after immune stimuli and a significant effect on rejection of the skin graft. Although these results are of interest, toxicity of methoxy-2 ethanol will be a limiting factor for therapeutic use.

[Tiopronine, new anti-rheumatic drug, has slow action in rheumatoid arthritis]. / La tiopronine, nouvel anti-rhumatismal a action lente dans la polyarthrite rhumatoïde.

2 mercapto propionyl glycine (tiopronine) has, like D-penicillamine, a thiol radicle; it is a powerful chelating agent of heavy metals. This analogy suggests that it may be used in rheumatoid arthritis. A preliminary double blind study lasting four months comparing 1g./day in 20 patients and a placebo in 10 patients showed slight (non significant) efficacy concerning all parameters. An open study using 1.5 g. daily is being carried out in 32 patients, and we note a beneficial effect on the morning stiffness, the joint index, the functional index, the prehension strength, the E.S.R., and the joint swelling. The side effects are similar to those of D-penicillamine: loss of taste, proteinuria, mucous ulceration, which required stopping treatment. The therapeutic effect within 4 months and was maintained for 18 months in the 15 patients under treatment. A new double blind trial comparing placebo and tiopronine at a dose of 1.5 g. daily is in progress.