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)

The results of long-term administration of leuprorelin acetate depot (TAP-144-SR), a sustained-release preparation of luteinising hormone-releasing hormone (LH-RH) agonist, to 40 stage D prostate cancer patients who had had no previous hormonal therapy, have been analyzed. The drug was administered by subcutaneous injection once every four weeks at a dose of 3.75 or 7.5 mg. The mean duration of treatment was 480 (141-1,266) days, and treatment continued for more than one year for 60% of the 40 patients. Objective response was evaluated in accordance with Japanese Response Criteria. The best objective response in the overall evaluation was a partial response in 68.6% of the total patient group (3.75 mg, 64.3%; 7.5 mg, 71.4%). During the administration period, 21 patients were diagnosed as having progressive disease (PD), and the mean time to onset of PD was 308 days. The earliest diagnoses of PD were made on bone metastases (17 cases) and prostatic acid phosphatase levels (12 cases). The survival rate, as determined by Kaplan-Meier's method, was 81.2% (3.75 mg, 80.5%; 7.5 mg, 81.3%) two years after starting the regimen and 66.0% (3.75 mg, 65.1%; 7.5 mg, 66.0%) after three years. There was no dose dependency between either of the two drug doses, which we adopted as functions of the objective response rate, and patients' survival. Serum levels of testosterone, LH and follicle-stimulating hormone (FSH) were monitored from the first-dose until the 148th week of administration. In all patients receiving the drug as scheduled, the testosterone level was maintained at less than 1 ng/ml, and the LH and FSH levels were maintained at levels lower than their respective upper normal limits. There were no particular adverse reactions specific to the long-term administration subsequent to the foregoing 12-week administration study. In conclusion, LH-RH analogue treatment is thought to be a long-lasting, effective, palliative measure for patients with previously-untreated, advanced, prostatic cancer.
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PMID:Long-term clinical study on luteinising hormone-releasing hormone agonist depot formulation in the treatment of stage D prostatic cancer. The TAP-144-SR Study Group. 151 66

The quality of life (QOL) was studied on 31 prostatic cancer (PC) patients, being followed at our out-patient-clinic during a relapse-free period. Fifteen of them were under treatment with a slow releasing LH-RH analogue (TAP-144 SR Depot) (TAP) and the other 16 prostatic cancer patients with synthetic estrogen (Honvan) (DES). The QOL of 37 benign prostatic hyperplasia (BPH) patients on conservative treatment was also studied. Concerning their general feeling of health, the prostatic cancer patients on TAP treatment felt subjectively better than those on DES. The social life of the patients on TAP or those who had BPH was less affected than that of those on DES. The quality of sexual life was worse for the prostatic cancer patients on both TAP and DES treatment than for the BPH patients.
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PMID:[A comparison of the quality of life of prostatic cancer patients under slow releasing LH-RH analogue (TAP-144SR Depot) treatment or synthetic estrogen treatment]. 178 8

A sensitive method for the determination of leuprorelin (TAP-144), a luteinizing hormone-releasing hormone analogue, and its C-terminal metabolite, M-I, in serum and urine has been developed. Leuprorelin and M-I were extracted from serum or urine samples with Sep-Pak C18 cartridges, and separated completely by high-performance liquid chromatography and determined by radioimmunoassay using [125I]leuprorelin as the labelled antigen. The detection limit of the method was 0.05 ng/ml for leuprorelin and M-I, and the recovery of the compounds added to serum and urine was over 88% with a coefficient of variation (within-assay) of less than 5%. The method was applied to the determination of leuprorelin and M-I-like immunoreactivity in serum or urine after administration of once-a-month injectable microspheres of leuprorelin acetate (TAP-144-SR) to patients with prostate cancer.
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PMID:High-performance liquid chromatography followed by radioimmunoassay for the determination of a luteinizing hormone-releasing hormone analogue, leuprorelin, and its metabolite. 190 42

TAP-144-SR is a sustained release formulation of an LH-RH agonist, leuprorelin acetate (TAP-144), that has been newly developed in Japan. As a phase I study, a single subcutaneous dose of TAP-144-SR was given to 15 patients with prostatic cancer to investigate the safety, endocrinological effects, and serum levels of the drug. The patients were divided into four groups according to the dosage levels of 1.88 mg, 3.75mg, 7.5 mg and 15 mg. No serious side effects were noted in any of the patients treated with any dose. No patients exhibited signs of a local reaction at the site of injection. In two patients transient exacerbation of clinical symptoms owing to "flare up" was observed. Serum testosterone levels decreased to the castration level (less than 1.0 ng/ml) in all of the patients, although the time required to attain the castration level tended to be longer in the patients receiving 1.88 mg. Serum TAP-144 levels increased on the first day and gradually decreased thereafter. In the groups of patients that received 3.75 mg or more of TAP-144-SR, TAP-144 was detected in the serum up to 4 weeks after administration. Based on the results of the phase I study, 3.75 mg and 7.5 mg of TAP-144-SR were selected as the doses for the phase II study. The phase II study was carried out as a multi-center open trial. Patients with stage B-D prostatic cancer received subcutaneously either 3.75 mg (3.75 mg group) or 7.5 mg (7.5 mg group) of TAP-144-SR once every 4 weeks for a total of 3 doses over a period of 12 weeks. TAP-144-SR 3.75 mg was administered to 51 patients and 7.5 mg to 50 patients. Both of these doses were adequate to suppress serum LH and FSH levels. Serum testosterone was decreased to the castration level within 22 days after the first dose, and this suppression was maintained throughout the treatment period. Clinical response rate (CR + PR) was 21% in the 3.75 mg group and 22-24% in the 7.5 mg group according to the Criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria. The response rate by the criteria of Japanese Prostatic Cancer Study Group was 51% in the 3.75 mg group and 62% in the 7.5 mg group. Adverse reactions were noted in 26% of patients in the 3.75 mg group and 34% in the 7.5 mg group.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Clinical phase I and phase II study on a sustained release formulation of leuprorelin acetate (TAP-144-SR), an LH-RH agonist, in patients with prostatic carcinoma. Collaborative++ Studies on Prostatic Carcinoma by the Study Group for TAP-144-SR]. 212 12

The hormonal and clinical efficacy of (D-Leu6)-des Gly-NH2(10)-LH.RH ethylamide (Leuprolide, TAP 144) was investigated with 12 prostatic cancer patients. The hormonal studies were performed in 8 patients who were not previously treated by any hormonal therapies including estrogen, castration and others. Serum level of LH and FSH was apparently decreased at the end of 2 weeks after the starting of leuprolide (1 mg/day) subcutaneous injection. At the same time, testosterone level was decreased to the castration level. Clinical efficacy of 1 mg/day of leuprolide was evaluated in 7 patients who were not previously treated. Three of the 4 patients with stage B2 cancer showed a partial response and 1 patient a stable response; and 1 of the 3 patients with stage D2 cancer showed a partial response and patients stable a response. No significant side effects were observed in these 12 patients. These results show that 1 mg/day of leuprolide has the same degree of potency in decreasing the serum testosterone as 20 mg/day.
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PMID:[Hormonal and clinical efficacy of (D-Leu6)-des Gly-NH2(10)-LH.RH ethylamide against prostatic cancer]. 293 56

A slow-release formulation of the luteinizing hormone releasing hormone (LH-RH)analog(TAP-144-SR) was administered in 6 cases of prostatic cancer. Five were untreated cases, 3 of moderately-differentiated and 2 of poorly-differentiated cancers (four D2 and one C, NX), the other (D2) was under control by another LH-RH analog. The plasma level of luteinizing hormone and follicle stimulating hormone fell below normal, and the plasma testosterone was less than 1 ng/ml by four weeks after start of treatment. According to the National Prostatic Cancer Project Criteria, 2 of the untreated cases showed a partial response and 3 of the untreated ones showed a stable response, one of which underwent transurethral resection later. The pretreated case still continued controlled more than 4 months. No side effect was noticed.
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PMID:[Treatment of prostatic cancer with slow-release formulation of luteinizing hormone releasing hormone (LH-RH) analog]. 313 36

Leuprolide (Lupron, TAP Pharmaceuticals), a potent agonist analogue of GnRH, has been shown to suppress testicular androgen production in animals. In order to determine the potential of leuprolide as an alternative to surgical castration in human males with prostatic cancer, this agent was administered to castrate and noncastrate males with carcinoma of the prostate. Baseline and treatment levels of LH, FSH, testosterone and dihydrotestosterone were determined serially. Leuprolide suppressed pituitary production of LH and FSH and, consequently, testicular production of testosterone and dihydrotestosterone. This agent simulates the results achieved with surgical castration.
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PMID:Evaluation of synthetic agonist analogue of gonadotropin-releasing hormone (leuprolide) on testicular androgen production in patients with carcinoma of prostate. 391 77

Observations that serum follicle-stimulating hormone (FSH) levels begin to rise after initial suppression during chronic gonadotropin-releasing hormone (GnRH) agonist treatment of men with prostate cancer had led to speculation that FSH escape might in part account for the failure of GnRH agonist analogs to completely suppress spermatogenesis in normal eugonadal men. However, previous studies in healthy young men failed to report FSH escape during GnRH agonist treatment for up to 16 weeks. We considered the possibility that this may have been due to the insensitivity of the FSH assays. Accordingly, using highly sensitive and specific two-site directed fluorometric assays and a sustained-release GnRH agonist formulation, we reexamined the issue of whether serum FSH levels rise after initial suppression during chronic GnRH agonist treatment. Two groups of healthy normal men, 19-50 years of age, received 7.5 mg of a long-acting GnRH agonist microcapsule formulation (Lupron Depot; TAP Pharmaceutical Company, North Chicago, Illinois) on days 1 and 30. In addition, the subjects received either 4 or 8 mg/day testosterone replacement by means of a testosterone microcapsule injected intramuscularly on day 1. Serum luteinizing hormone (LH) and FSH levels were measured by sensitive and specific two-site directed fluorometric assays on multiple occasions during the 3-week control period and the 9-week treatment period. Serum LH levels declined to a nadir between 2 and 4 weeks and stayed suppressed throughout the remainder of the treatment period in both the 4- and 8-mg testosterone groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Follicle-stimulating hormone (FSH) escape during chronic gonadotropin-releasing hormone (GnRH) agonist and testosterone treatment. 786 Apr 18

Between January 1996 and June 2000, 192 men with prostate cancer underwent radical retropubic prostatectomy (RP) and bilateral pelvic node dissection in 26 centers participating in the Italian randomized prospective TAP study. The reviewing pathologist evaluated 145 RP specimens. Seventy-five cases had not been treated with total androgen ablation before RP was performed, whereas 70 had been treated for three months. Whole-mount sectioning of the complete radical prostatectomy specimens was adopted in each center for accurately evaluating the pathological stage of prostate cancer and resection limit status. The results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage T2 because of the significant pathological down-staging and decrease in the number of positive margins in the RP specimens. On the basis of the experience acquired through the Italian TAP study and recent publications on prognostic factors in prostate cancer, the original practice protocol for examination of RP specimens removed from patients with carcinoma of the prostate glands was updated.
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PMID:Surgical pathology examination of radical prostatectomy specimens. Updated protocol based on the Italian TAP study. 1184 30

TAP-144-SR (3M) is a 3-month sustained releasing injection of a super-active agonist of luteinizing hormone releasing hormone (LH-RH), leuprorelin acetate. At the Department of Urology of Gunma University Hospital, TAP-144-SR (3M) was injected once subcutaneously into 10 prostatic cancer patients who had had no treatment in the past to investigate safety, serum testosterone levels, drug concentrations and efficacy. In safety, no problematic adverse reactions occurred, and the drug was well tolerated. Serum testosterone levels elevated temporarily up to 2 days after injection and then were reduced rapidly. The levels were reduced below the castration level (100 ng/dl) after 3 weeks and then remained reduced up to 12 weeks. Serum TAP-144 levels including metabolite M-I, elevated to maximal plasma concentration up to 3 hours after injection and then were maintained at about 0.2 ng/ml between 1 week and 12 weeks after injection. With respect to the anti-tumor effects, the response rate according to "criteria of prostate cancer" at 12 weeks after injection was 100% (stable response cases) and the ratio of PSA normalization at 12 weeks was 90%. These results showed that an injection of TAP-144-SR (3M) was well tolerated in prostate cancer patients having no prior treatment and inhibited serum testosterone persisting for at least 12 weeks so that TAP-144-SR (3M) was concluded to be safe and clinically effective for prostate cancer patients.
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PMID:[Clinical effects of a 3-month formulation LH-RH agonist, TAP-144-SR (3M) in prostate cancer patients]. 1261 15


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