PURPOSE: We evaluated the therapeutic effect of combined androgen blockade (CAB) compared with that of medical, or surgical, castration monotherapy, in the treatment of the metastatic prostate cancer. MATERIALS AND METHODS: Of 53 patients with metastatic prostate cancer, we compared the overall survival between CAB and monotherapy groups, using a Kaplan-Meier survival curve. We also compared the therapeutic effect of flutamide and bicalutamide in the CAB group. RESULTS: There were no differences in known prognostic factors between the CAB and monotherapy groups. The mean survival after treatment were 43 months in the CAB group, and 38 months in monotherapy group, with no significant difference (p=0.470). There were also no differences in the survival rates between the flutamide and bicalutamide groups (p=0.158). CONCLUSIONS: These results implicate that the CAB was no better than medical, or surgical, castration monotherapy in patients with metastatic prostate cancer, and that flutamide or bicalutamide, in CAB, resulted in similar efficacies and tolerabilities.
Castration ; Flutamide ; Humans ; Neoplasm Metastasis ; Prostate* ; Prostatic Neoplasms* ; Survival Rate

PURPOSE: We evaluated the therapeutic effect of combined androgen blockade (CAB) compared with that of medical, or surgical, castration monotherapy, in the treatment of the metastatic prostate cancer. MATERIALS AND METHODS: Of 53 patients with metastatic prostate cancer, we compared the overall survival between CAB and monotherapy groups, using a Kaplan-Meier survival curve. We also compared the therapeutic effect of flutamide and bicalutamide in the CAB group. RESULTS: There were no differences in known prognostic factors between the CAB and monotherapy groups. The mean survival after treatment were 43 months in the CAB group, and 38 months in monotherapy group, with no significant difference (p=0.470). There were also no differences in the survival rates between the flutamide and bicalutamide groups (p=0.158). CONCLUSIONS: These results implicate that the CAB was no better than medical, or surgical, castration monotherapy in patients with metastatic prostate cancer, and that flutamide or bicalutamide, in CAB, resulted in similar efficacies and tolerabilities.
Castration ; Flutamide ; Humans ; Neoplasm Metastasis ; Prostate* ; Prostatic Neoplasms* ; Survival Rate

PURPOSE: The purpose of this study was to evaluate cycling change and characteristics of treatment in patients receiving intermittent androgen suppression (IAS). MATERIALS AND METHODS: From May 1995 to April 2001, we retrospectively reviewed 28 cases of prostate cancer patients treated with IAS. Treatment was initiated with goserelin acetate with flutamide and continued until serum PSA nadir was observed. Medication was then withheld till the serum PSA increased to a predetermined level. This cycle of treatment and no-treatment was repeated until the regulation of PSA became androgen independent. RESULTS: Patients have completed at least one, and up to four treatment cycles. Mean nadir serum PSA level was 0.69ng/ml, 0.70ng/ml, 1.15ng/ml, 2.64ng/ml for each cycle, and was reached within average 4.7 (2-8) months after beginning treatment. Patients spent an average of 42% of the time not receiving therapy, but the time off therapy decreased as the number of treatment cycles increased. In most cases, side effects related with androgen suppression was improved during off-treatment. CONCLUSIONS: IAS appears to be a possible treatment option in patients with prostate cancer. This approach could result in reduced toxicity and cost of treatment and affords an improved quality of life when the patient is off therapy.
Flutamide ; Goserelin ; Humans ; Prostate* ; Prostatic Neoplasms* ; Quality of Life ; Retrospective Studies

PURPOSE: Flutamide (4-nitro-3-t-trifluoromethyl-isobutyranilide) is an androgen-receptor antagonist with typical antiandrogenic effect, used to treat androgen-dependent disorders such as prostate cancer. However, some reports noted that flutamide has direct effects to neuronal cells. It has been shown to retard the development of electrical kindling in rats. METHODS: We used the chemoconvulsant 4-aminopyridine (4-AP) and picrotoxin (PTX) in the in vitro hippocampal slice model to determine of flutamide for the suppression of epileptiform discharges. Extracellular field potential recordings were obtained from the CA3 pyramidal layer of hippocampus. RESULTS: The concentration of 30 and 100 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 57.8% and 66.8% each compared with the 4-AP only slices. In 100 micrometer PTX, 10 and 30 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 56.6% and 82.5% each. Intermixed with flumazenil, the anticonvulsant effect of flutamide was decreased. CONCLUSIONS: Flutamide suppressed epileptiform discharges induced by 4-AP and PTX in vitro seizure model. It suggests that flutamide influence to anti-epileptic activity by benzodiazepine site of the GABAA receptor.
4-Aminopyridine ; Benzodiazepines ; Flumazenil ; Flutamide ; Neurons ; Picrotoxin ; Prostatic Neoplasms ; Seizures

PURPOSE: The purpose of this study was to evaluate the feasibility of using intermittent androgen deprivation(IAD) in patients with prostate cancer. MATERIALS AND METHODS: We reviewed the medical records of 29 patients treated with IAD for prostate cancer. Androgen deprivation with goserelin and flutamide was continued for at least 4 months after serum prostate specific antigen(PSA) became undetectable or a nadir level was reached. Medication was then discontinued until serum PSA reached a predetermined level. This cycle of treatment was repeated until there was evidence of androgen independence. RESULTS: Twenty-one patients completed the on-treatment during cycle 1, with a median time to PSA nadir of 3 months. Nine patients completed cycle 1 with a median time of off-treatment of 11 months(38% of a treatment cycle). Eight patients continued the off-treatment during cycle 1 for 1+ to 8+ months. During cycle 2, 3 patients achieved a PSA nadir in a median time of 3.5 months. While off treatment, most patients reported reduction of symptoms associated with androgen suppression. CONCLUSIONS: IAD is a feasible alternative for continuous androgen deprivation for treatment of prostate cancer. It also results in the reducion of toxicity, cost of treatment, and possibly a delay in tumor progression.
Flutamide* ; Goserelin* ; Humans ; Medical Records ; Pilot Projects* ; Prostate* ; Prostate-Specific Antigen ; Prostatic Neoplasms*

Flutamide, an oral nonsteroidal, antiandrogenic, anilid compound which inhibits the uptake and binding of androgens to nuclear receptors in the prostate, is used with or without LH-RH analogues for treatment of patients with metastatic carcinoma of the prostate. Clinically significant hepatotoxicities such as toxic hepatitis, cholestatic hepatitis, hepatic failure, and even death have rarely been reported in the English literature, but no case has been reported in Korea. A 75-year-old man with metastatic carcinoma of the prostate had taken flutamide (750 mg/day) for 7 months and suddenly developed jaundice and general weakness. The findings of blood chemistries were compatible with cholestatic hepatitis, but ultrasonography, viral marker and auto-antibody studies did not reveal any attributable causes. Histologic examination of a sono-guided liver biopsy only disclosed centrilobular cholestasis, nuclear glycogenosis and mild sinusoidal lymphocytic infiltration. Discontinuation of flutamide resulted in an almost full recovery of the patient's liver function in 2 months. We, herein, report a case of flutamide-induced acute choestatic hepatitis with a brief review of the literature.
Acute Disease ; Aged ; Androgen Antagonists/*adverse effects ; Case Report ; Cholestasis/*chemically induced ; Flutamide/*adverse effects ; Hepatitis, Toxic/*etiology ; Human ; Male

OBJECTIVETo establish a mouse model of hypospadias induced by flutamide to further studying molecular mechanisms of hypospadias etiology.

METHODSEighty timed pregnant ICR mice were randomly divided into four groups. Flutamide was injected subcutaneously (s.c.) with mixture sesame oil at 0 (Group A), 25 (Group B), 50 (Group C), 100 (Group D) mg.kg-1.d-1 from GD (gestation days) 12 to 16, respectively. The fetuses of two pregnants from each group were anatomized to observe the position of testes and the development of prostates on the day of delivery. Urethras and the position of testes were examined on postnatal day 28.

RESULTSHypospadias was seen in Group A (0), B (44.2%), C (92.7%) and D (100%), and cryptorchidism in Group A (0), B (4.8%), C (23.2%) and D (32.4%), respectively. Flutamide caused 100% incidence of prostate agenesis in Group C and D and 19.2% in Group B, and 100% incidence of female-like anogenital distance in Group B, C, and D.

CONCLUSIONThe experimental model of hypospadias induced by flutamide is steadier and more suitable for popularization.

Androgen Antagonists ; toxicity ; Animals ; Disease Models, Animal ; Female ; Fetus ; drug effects ; Flutamide ; toxicity ; Hypospadias ; chemically induced ; Male ; Mice ; Pregnancy

PURPOSE: To investigate involvement of chronic estrogen deficiency in impairment of relaxation response of the clitoral cavernous smooth muscle. MATERIALS AND METHODS: New Zealand white female rabbits were randomly divided control (sham operation, n=6) and experimental groups; 1) bilateral oophorectomy (n=8), 2) oophorectomy with estradiol replacement (n=7), 3) oophorectomy with flutamide treatment (n=6). All the rabbits were sacrificed 12 weeks after the operations. Blood levels of estradiol and lipid fractions were measured just before the operations and sacrifice. Clitoral cavernous strips were obtained to observe relaxation responses to endothelium-dependent and -independent vasodilators, and electrical field stimulation (ESF). RESULTS: The uterus weight and serum estradiol level decreased significantly (p<0.01) in the oophorectomy group compared with the baseline data. The serum levels of total cholesterol, triglyceride, and low density lipoprotein increased significantly (p<0.01) in the oophorectomy group. The relaxations of the clitoral strips to acetylcholine were significantly attenuated in the oophorectomy group compared with those of the control and estrogen replacement groups. However, sodium nitroprusside- and nonadrenergic noncholinergic-induced relaxations were not significantly different among the 4 groups. No significant histologic changes were noted in the clitoral tissues of the oophorectomy group. CONCLUSIONS: Chronic estrogen deficiency in the rabbits may cause impairment of endothelium-dependent relaxation of clitoral corpus cavernosal smooth muscles. Further studies are needed to determine whether the hypoesterogenemia itself and/or secondary hypercholesterolemia due to the chronic estrogen deficiency may result in the impairment.
Acetylcholine ; Cholesterol ; Estradiol ; Estrogen Replacement Therapy ; Estrogens ; Female ; Flutamide ; Humans ; Hypercholesterolemia ; Lipoproteins ; Muscle, Smooth* ; New Zealand ; Ovariectomy ; Rabbits ; Relaxation* ; Sodium ; Triglycerides ; Uterus ; Vasodilator Agents

The search for nonhormonal pharmacological agents capable of reducing out flow obstruction caused by benign prostatic hyperplasia (BPH) began in the 1970s when alpha adrenergic receptors were demonstrated within the smooth muscle element of prostatic adenomas, the prostatic capsule, and the bladder neck. Recently, many studies have confirmed that the alpha adrenoceptor blockade sub-jectively and objectively reduces symptoms and urodynamic parameters in bladder outflow obstruction. Very longterm effects of the alpha blockade upon the pro-state are not yet known. There is no direct evidence of a decrease in the stromal smooth muscle bulk or in the total prostate volume after longterm treatment with alpha adrenoceptor blockers in man. The endocrinebased therapies, such as stilbestrol, luteinizing hormonereleasing hormone analogues, antiandrogens flutamide, and cyproterone acetate, have sometimes been used to treat BPH, but with a limited efficacy and prominent sideeffects such as loss of libido, impotence, hot flushes, and gynecomastia. Although it has been shown that some of these therapies may shrink the prostate, the sideeffects are intolerable to most patient. On the other hand, new 5 alpha reductaseinhibiting agents are able to block the effects of androgen within the prostate without a systemic antiandrogen activity. Since the effects of androgens are particularly directed at the glandular element of the prostate rather than at the smooth muscle, the combined use of alphaadrenoceptor blockers and 5 alphareductase inhibitors could theoretically produce an additive effect in the treatment of BPH. The indications of medical treatment for BPH include patients with mild to moderate symptoms, especially if they are reluctant to undergo surgery, and those who are not medically eligible to surgery.
Androgen Antagonists ; Androgens ; Cyproterone Acetate ; Diethylstilbestrol ; Erectile Dysfunction ; Flutamide ; Gynecomastia ; Hand ; Humans ; Libido ; Lutein ; Male ; Muscle, Smooth ; Neck ; Prostate ; Prostatic Hyperplasia* ; Receptors, Adrenergic, alpha ; Urinary Bladder ; Urodynamics

PURPOSE: The incidence of flutamide-related liver toxicity was studied in 56 korean patients, treated for advanced prostate cancer with flutamide combined with a LHRH agonist or orchiectomy. MATERIALS AND METHODS: Serum glutamic oxaloacetic transaminase(SGOT), serum glutamic pyruvic transaminase(SGPT), total bilirubin and alkaline phosphatase were measured to assess liver function at baseline, 1, 2 and 3 months and every 3 months thereafter. When they were elevated three-fold or more than upper normal levels, we regarded it as a presence of liver toxicity. Viral marker studies (Hepatitis B, C) were performed in patients with elevated SGOT and/or SGPT after flutamide administration. RESULTS: Ten patients(17.9%) showed elevated SGOT and/or SGPT at an average of 3 months after flutamide administration. All patients who performed viral marker studies revealed negative results. Total serum bilirubin was elevated in three(5.4%) patients and clinical jaundice appeared in one(1.8%). All clinical and biochemical manifestations of liver toxicity disappeared within two months after discontinuation of flutamide and no sequelae was observed for 15 months. CONCLUSIONS: The Incidence of flutamide-Induced hepatotoxicity seems to be higher In Korea than in North America. But this might not be due to the fact that Korea is an endemic area of viral hepatitis. Further study will be necessary for the verification of dose-related toxicity of flutamide in Korean prostate cancer patients. We recommend liver function test periodically to patients treated with flutamide.
Alanine Transaminase ; Alkaline Phosphatase ; Aspartate Aminotransferases ; Bilirubin ; Biomarkers ; Flutamide ; Gonadotropin-Releasing Hormone ; Hepatitis ; Humans ; Incidence* ; Jaundice ; Korea* ; Liver Function Tests ; Liver* ; North America ; Orchiectomy ; Prostate* ; Prostatic Neoplasms*