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*

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

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

AIMTo study the secretory activity and androgen regulation of glutathione peroxidase (GPx) in epithelial cell cultures from human epididymis.

METHODSTissue was obtained from patients undergoing therapeutic orchidectomy for prostatic cancer. Epithelial cell cultures were obtained from the caput, corpus and cauda epididymides. Enzymatic activity was measured in conditioned media by colorimetric methods in absence or presence of 1, 10 or 100 nmol/L testosterone. The effect of 1 micromol/L flutamide was also evaluated.

RESULTSGPx activity was higher in cultures from corpus and cauda than caput epididymidis. The presence of different concentrations of testosterone increase enzyme activity in cell cultures from all epididymal regions. Addition of flutamide reverses the androgen dependent increase of GPx activity.

CONCLUSIONGPx activity is secreted from human epididymal cells in a region dependent manner and is regulated by androgens.

Aged ; Androgen Antagonists ; pharmacology ; Cell Culture Techniques ; Epididymis ; enzymology ; Flutamide ; pharmacology ; Glutathione Peroxidase ; drug effects ; metabolism ; Humans ; Male ; Middle Aged ; Testosterone ; metabolism

OBJECTIVETo understand long-term survival rate after combined androgen blockade (CAB) in patients with advanced prostate cancer.

METHODSA selected population of 59 patients with advanced prostate cancer were treated with CAB. 28.81% (17/59) of patients had clinical locally advanced disease (stage T3-4N0M0), and 45.76% (27/59) of patients had metastatic disease (stage TxNxM+). Overall, patients were followed for a median of 62 (range 6-136) months.

RESULTSOf the 59 patients with advanced prostate cancer, 3-year, 5-year and 7-year overall survival rates were 79.36%, 61.46% and 49.15%, respectively. The 5-year survival rate were 80.77% and 32.65% for clinical locally advanced disease and metastatic disease. Specifically, men with poorly differentiated prostate cancer had a 5-year survival of only 30% when compared with men with well-differentiated prostate disease who had a 5-year survival of 86.21%.

CONCLUSIONBased on these findings, men with poorly differentiated cancer, stage T3c-4NxMx or TxNxM+ and PSA level above 30 microg/L had a high probability of dying from their advanced prostate cancer.

Aged ; Androgen Antagonists ; therapeutic use ; Combined Modality Therapy ; Flutamide ; therapeutic use ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms ; drug therapy ; mortality ; surgery ; Survival Rate

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