Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Flutamide (4'-nitro-3'-trifluoromethylisobutyranilide) has a pronounced effect on the delta 4-3-ketosteroid 5-reductases of cortisol in man. The urinary metabolites isolated following 4-14C-cortisol administration to men with prostatic cancer treated with flutamide indicate decreased activity of the 5 beta-reductase with increased activity of 5 alpha-reductase. The alternate pathway of cortisol metabolism to the cortols and cortolones via Reichstein's substances epi E and Epi U is enhanced.
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PMID:Further studies on the effects of flutamide on cortisol metabolism. 737 19

A case is presented of a middle-aged man suffering from stage D2 prostate cancer with pulmonary metastases who responded favorably, first, to endocrine combination therapy with the antiandrogen flutamide and an LHRH agonist for 5.5 years, and, second, to the subsequent withdrawal of Flutamide at the time of the progression of the disease. This case has several exceptional features: absence of bone metastases, pulmonary metastatic nodules characterized as focal neuroendocrine differentiation, and a positive response to antiandrogen withdrawal upon relapse of metastases after initial positive response. The concept of escape to androgen blockade and development of androgenic hypersensitivity is discussed.
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PMID:Metastatic prostate cancer pulmonary nodules: beneficial effects of combination therapy and subsequent withdrawal of flutamide. 751 17

The optimal treatment of prostate cancer in clinical stage C is controversial. On the one hand a disease still confined by definition, as stage C is, should require a curative therapy such as surgery or radiotheratherapy. On the other hand the known fact that 50% of stages C are pathological stages D1, should propose a palliative, even thou effective, medical treatment. In fact both choices are questionable. A radical treatment risks being insufficient, whereas a palliative does not allow for giving a chance of a theoretically possible cure. In an attempt to resolve this difficulty, a sort of compromise is proposed. The patients should be initially treated with radical radiotherapy, and only in the case of progression will standard hormonotherapy be given. Thanks to this behaviour a possibility of cure is maintained, and, in addition, when suffering a progression the patients are likely to benefit from hormonotherapy owing to the fact that they are not pretreated. From 1985 to 1991 forty-eight clinical stage C patients were observed. They were given the choice between two treatments after explaining the theoretical benefits and disadvantages of both. Treatment A consisted of cobalt-60 therapy followed by hormonotherapy after progression, treatment B in primary ormonotherapy with LH-RH analogue +/- Flutamide. Twenty patients opted for treatment A and 21 for B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of prostatic carcinoma in clinical stage C. Comparison between radiotherapy plus hormonal therapy after progression and immediate hormonal therapy]. 797 84

The main goal of hormonotherapy in management of locally advanced or metastatic prostate cancer is the control over the progression of the neoplastic disease rather than a possible benefit to the primary lesion. Nevertheless during hormonal treatment an evident decrease of prostatic volume can often be noted even though its clinical meaning has rarely been investigated. In order to evaluate a possible correlation between local modifications and prognosis, a retrospective analysis of a group of patients on hormonotherapy was performed. From March 1987 to March 1991, 98 patients with clinical stage C and D2 prostate cancer were treated. Fifty two of them were considered eligible for assessing local response because they had had neither surgery nor radiotherapy over the prostate; moreover their pre-treatment prostatic volume, as assessed by US scan, exceeded 22 ml. Out of these patients 24 were given Goserelin every 4 weeks and the remaining 28 added Flutamide at the dose of 750 mg per day. The prostatic volume was assessed quarterly and considered as response if decreased more than 35% of pretreatment value or as progression if increased over 25% of immediately previous value. In both cases the result needed to be confirmed three months later, but it was registered when first observed. After a mean follow-up of 32.4 +/- 18.7 months a local response occurred in 44 patients (84.6%) during a period ranging 3 to 18 months. Eight patients did not show a prostatic volume decrease and 4 suffered of local progression. In these latter cases the local progression coincided with distant progression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical significance of the local response to prostatic carcinoma during hormonotherapy]. 802 25

Rat transplantable prostatic tumors (Dunning R-3327) were treated with flutamide before tumors grew palpable, in order to examine the effect of short term treatment of antiandrogen for prostatic cancer in latent period on the growth after appearance of tumor. Flutamide delayed an appearance of the tumor nodule and retarded the growth rate in proportion as treatment began earlier. Flutamide also reduced final tumor volume. Flutamide-treated tumors histologically consisted of small or dilated glandular structure with an increase in stromal area, but androgen receptors were preserved. Flutamide-treated tumor showed slow growth with androgen sensitivity when transplanted to intact rats, showing prolonged influences of antiandrogen on tumor growth. There was no significant difference between flutamide-treated and control groups in weight of accessory sex organs and serum androgen or estrogen levels. In conclusion, flutamide treatment may retard an appearance of prostatic cancer concomitant in benign prostatic hyperplasia.
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PMID:Effect of early exposure of flutamide on subsequent growth of transplantable rat prostatic tumor (dunning R-3327). 814 68

Flutamide was administered to a patient in conjunction with orchiectomy for stage D2 prostate cancer. Subsequently, profound neutropenia developed with a neutrophil count of 0.28 x 10(9)/l. Bone marrow aspirate showed granulocyte hypoplasia and maturation arrest consistent with drug induced injury. Neutrophil count returned to normal after discontinuation of flutamide and administration of a short course of granulocyte colony-stimulating factor. Other medications were continued with no effect on neutrophil count. The appearance of the bone marrow and the return of neutrophils after the discontinuation of flutamide indicate that flutamide may have contributed to neutropenia.
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PMID:Severe reversible neutropenia following treatment of prostate cancer with flutamide. 815 86

Although treatment of intact adult male rats with the pure antiandrogen flutamide or a luteinizing hormone-releasing hormone (LHRH) agonist alone leads to partial inhibition of ventral prostate weight, maximal inhibition is achieved by combination of the two drugs. Potentializing effects of the two compounds were observed even on prostatic ornithine decarboxylase activity. Because LHRH agonists are widely used to achieve medical castration in men treated for prostate cancer, it is of interest to observe that in the dog, known for being the best model for studies of the action of LHRH agonists, flutamide does not interfere with the potent desensitizing action of the LHRH agonist on pituitary LH secretion, thus supporting the combined use of flutamide with an LHRH agonist for maximal androgen blockade without loss of efficiency of the LHRH agonist. Because prostate cancer is known to show a high degree of heterogeneity of its sensitivity to androgens, we analyzed the effect of combined antiandrogen therapy on parameters more sensitive to androgens than ventral prostatic weight itself. In agreement with its pure antiandrogenic characteristics, flutamide alone has no stimulatory effect on the intraprostatic level of mRNA encoding the C1 or C3 component of prostatic binding protein (PBP), whereas cyproterone acetate (CPA), megestrol acetate (MEG), and, especially, medroxyprogesterone acetate (MPA) markedly stimulate PBP-C1 and PBP-C3 mRNA levels, an effect reversed by flutamide, thus further supporting the intrinsic androgenic activity of all these steroidal derivatives. Similar androgenic effects of the steroidal derivatives were observed on prostatic ornithine decarboxylase activity. Androgen-sensitive Shionogi tumor cells were then used to assess the antiandrogenic/androgenic properties of flutamide and the above-indicated steroidal derivatives. MPA, MEG, CPA as well as spironolactone-stimulated cell proliferation under both in vivo and in vitro conditions, thus illustrating the intrinsic androgenic activity of all these compounds. Flutamide was inactive by itself and reversed the stimulatory effect of all other compounds, thus indicating its pure antiandrogenic activity. Although castration reduces intraprostatic dihydrotestosterone (DHT) to undetectable levels in the rat and guinea pig, the concentration remains at about 50% of the value found in intact men after castration, thus indicating an important contribution of the adrenals to DHT in the human prostate, a finding that requires the addition of an antiandrogen to block the action of this important amount of DHT remaining after castration.
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PMID:Mechanism of action and pure antiandrogenic properties of flutamide. 825 97

Maximal androgen blockade may improve the effectiveness of treatment of prostate cancer. To test this hypothesis we conducted a randomized, double-blind trial in patients with disseminated and previously untreated prostate cancer (stage D2). All patients (n = 603) received leuprolide, 1 mg/day s.c. in combination with either placebo (n = 300) or flutamide 250 mg p.o. t.i.d. (n = 303). The median progression-free survival times were estimated at 14 months for the leuprolide plus placebo group and 17 months for leuprolide plus flutamide patients: median times for overall survival were 29 vs. 35 months, respectively. Patients with minimal disease and good performance status did particularly well on combination therapy. Median progression-free survival for this subgroup was 19 months for leuprolide plus placebo patients vs. 48 months for patients on combined therapy (p = 0.035) Flutamide appeared to reduce the disease flare associated with leuprolide monotherapy. Combined androgen blockade with leuprolide and flutamide is superior to leuprolide treatment alone in patients with disseminated prostate cancer.
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PMID:Total androgen blockade: the United States experience. 826 30

A phase I study of orally administered flutamide (a pure anti-androgen) was performed in 26 patients with prostatic cancer. No side effects were observed in 11 patients receiving single doses of either 125, 250, 375 or 500 mg. However, in the daily dosing schedule of 375, 750, 1125 and 1,500 mg/day doses, where medication was taken in three divided doses, discomfort in the stomach, nausea, vomiting and anorexia were experienced in one of the four patients receiving the highest dose of 1,500 mg. Nine patients receiving the other doses did not complain of toxic symptoms. Laboratory values did not change in the three patients receiving the lowest 375 mg/day dose, but elevation of transaminase was observed in five of the nine patients given higher doses. This elevation was observed in all the three patients receiving 1,500 mg/day dose. Among the serum hormone levels, significant increases of luteinizing hormone were observed. As for efficacy, objective responses were observed in two of the three patients in each of the four daily dosing groups. Improvement of pain, voiding obstruction symptoms, and performance status were also observed. Flutamide was found to be absorbed rapidly and to exist as a hydroxylated form (hydroxy-flutamide) in the plasma. The half-life of hydroxy-flutamide was similar in the single and daily administration, but the peak concentration and area under the concentration versus time curve in the daily administration became greater than those in the single administration. In conclusion, flutamide should be examined for efficacy and safety using doses of 375 to 1,125 mg/day in the phase II study.
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PMID:[Phase I study of flutamide, a nonsteroidal antiandrogen, in patients with prostatic cancer]. 850 38

Of 102 patients with metastatic prostate cancer, 52 were treated with orchidectomy and 50 with CHB; 22 of these received a LHRH analog + Flutamide and 28 orchidectomy + Flutamide. No differences were seen in either arm in terms of age (69.9 vs 70.2 years) or initial PSA (493.3 vs 486.5 ng/ml) variables. After three months treatment, CHB achieved a decrease of PSA higher than monotherapy (52.9 vs 34.5 ng/ml) p<0.01 as well as minimum PSA level during follow-up (41.2 vs 17.5 ng/ml) (p<0.001). Initial clinical response rates were higher in the group treated with complete blockade (42.3% vs 52%) (p=n.s.). Overall, no significant differences were seen between the actuarial curves of biological progression, clinical progression and survival, with expected mean values of 13 vs 12, 14 vs 15 and 34 vs 28 months, respectively. However, when survival was considered as a function of bone disease dissemination, a greater survival rate was seen in patients with minimal M1 disease (p<0.05), and there were no differences between the M2 and M3 arms.
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PMID:[Final results of complete hormone blockade versus monotherapy in prostatic metastatic cancer. PSA implications]. 866 27


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