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)

Inasmuch as treatments for advanced prostate cancer may have identical clinical outcomes but very different meanings to patients, we sought to compare the impact of surgical and medical castration (orchiectomy versus injected goserelin acetate Zoladex) on quality of life and psychosocial status. A total of 147 men with Stage D prostate cancer participated in the study: 115 selected treatment with goserelin acetate, and 32 chose orchiectomy. Quality of life, as measured by the Functional Living Index: Cancer (FLIC), improved at both the 3 and the 6 month follow-up in the goserelin acetate group (p = 0.0001), but did not change from baseline at 6 months in the orchiectomy group (p = 0.54). These findings were paralleled by improvement from baseline in psychosocial status, as measured by the Profile of Mood States (POMS), at 6 month follow-up (p = 0.01 in the goserelin acetate group versus p = 0.60 in the orchiectomy group). This investigation, which is among the first to evaluate patients' appraisals of their lives following treatment choices for advanced prostatic cancer, argues compellingly for including quality of life in assessments of therapy.
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PMID:Quality of life and psychosocial status in stage D prostate cancer. Zoladex Prostate Cancer Study Group. 129 64

Highly potent LH-releasing hormone (LHRH) agonists have been recently introduced in therapy for the treatment of the carcinoma of the prostate, an androgen-dependent pathology. These peptides are believed to act mainly by inhibiting the pituitary-testicular axis and, consequently, by reducing testosterone levels. The recent observation that binding sites for LHRH analogs are present on prostatic tumor tissue suggests that these drugs could also act directly on the tumor. To verify this hypothesis, the effects of two potent LHRH agonists [Zoladex (Z) and Buserelin (B)] have been studied on the proliferation of the human prostatic cancer cell line LNCaP (lymph node carcinoma of the prostate). LNCaP cells were treated for 9 days with different doses of either Z or B (concentrations from 10(-12)-10(-6) M). Both analogs significantly inhibited cell proliferation at doses between 10(-9)-10(-6) M. The antiproliferative action of the two LHRH agonists was shown to be dose dependent, with IC50 values of 0.82 and 1.79 nM for Z and B, respectively. A similar treatment with B was without any significant effect on the proliferation of a mouse embryo fibroblast cell line (Swiss 3T3), which was used as a nontumoral control. The inhibitory action of both LHRH agonists (10(-8) M) on LNCaP cell proliferation was completely antagonized by the simultaneous treatment of the cells with a potent LHRH antagonist (Nal-Arg-LHRH; 10(-8) M); when given alone at the dose selected, the antagonist did not affect cell growth. These results clearly suggest that the antiproliferative effect of LHRH agonists on LNCaP cells may be mediated by specific receptors. The presence of binding sites for [125I]B was consequently demonstrated on the membranes of LNCaP cells cultured in a medium containing charcoal-stripped fetal calf serum, i.e. in the absence of steroids. The affinity of these binding sites for the ligand was lower than that observed for the same receptors on rat pituitary membranes. To clarify the mechanism of the antiproliferative action of the LHRH agonists, the effects of both Z and B on the incorporation of [3H]thymidine and [14C]methionine into LNCaP cells were investigated. During a short incubation period (3 h), the two LHRH agonists rapidly inhibited [3H]thymidine incorporation into the cells. The same treatment did not affect the incorporation of [14C]methionine into proteins.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antiproliferative effects of luteinizing hormone-releasing hormone agonists on the human prostatic cancer cell line LNCaP. 132 49

An open randomised Phase III trial was conducted of the depot GnRH analogue goserelin (Zoladex) versus stilboestrol (3 mg/day) in patients with advanced or metastatic prostate cancer. The study included 250 patients and the median follow-up was 43 months. In the Zoladex arm the time to first response was achieved earlier and more patients reported an improvement in symptoms. There was no statistically significant difference between the Zoladex and the stilboestrol arms with regard to survival and time to treatment failure. A major reason for treatment failure was the preponderance of adverse events in patients receiving stilboestrol. It is suggested that stilboestrol should no longer be used for prostate cancer when equally effective alternative treatments are available.
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PMID:Phase III randomised study of zoladex versus stilboestrol in the treatment of advanced prostate cancer. 138 72

Use of polymeric drug delivery systems is rapidly becoming an established approach for improvement of cancer chemotherapy. Zoladex, a poly lactide-co-glycolide subcutaneous implant that delivers a luteinizing hormone releasing hormone analog over 28 days, is now the treatment of choice for prostate cancer, and a polyanhydride matrix containing BCNU is currently in phase III evaluation for treatment of glioma multiforme. Soluble polymers were first proposed as targetable drug carriers in the mid-1970s, and although the first conjugates are still at an early stage of development some, e.g. SMANCS (styrene maleic acid-neocarzinostatin) and monomethoxypolyethyleneglycolasparaginase, are now undergoing clinical evaluation and show considerable promise. Polymeric drug delivery systems are usually designed to produce an improved pharmacokinetic profile of an antitumor agent (controlled release) and in addition soluble carriers can achieve either first-order (organ specific) or second-order (tumor specific) drug targeting by virtue of the fact that they are usually administered intravenously and should theoretically access primary and secondary disease. Soluble polymeric carriers have the potential to improve the activity of conventional antitumor agents, peptide and protein drugs, and have recently been used in constructs for delivery of oligonucleotides. With increased awareness that the successful design of a polymeric drug delivery systems can only be achieved with prior consideration of the pathology and stage of the disease, tumor accessibility, biochemistry and cell biology of the target site, choice of appropriate therapeutic agent(s) and understanding of their fundamental mode of action, we have seen the emergence of a number of exciting and potentially more selective antitumor therapies based on polymer technologies. Here, the basic principles for design of soluble polymeric drug delivery systems are explained and illustrated using examples drawn from our studies on the development of N-(2-hydroxypropyl)methacrylamide copolymer conjugates for use in cancer chemotherapy. Those soluble polymeric carriers that are undergoing clinical evaluation are briefly reviewed.
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PMID:Drug-polymer conjugates: potential for improved chemotherapy. 152 99

PSA is an important tumor-marker for prostatic cancer disease. We developed a sensitive, simple and inexpensive Sandwich ELISA for PSA with two monoclonal antibodies. The precision and reliability of the assay are reflected in the low inter- and intraassay coefficient of variation. PSA was not detectable in sera from normal females (n = 50). Sera from males with different serum levels of PSA (normal males, patients with prostate hypertrophy, prostate cancer patients, n = 79) and 15 prostate cancer patients treated with Zoladex were measured by our ELISA and by a commercially available RIA. The correlation coefficient between these both test systems was close to 1 (r = 0.97).
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PMID:Development and evaluation of an enzyme-linked immunoassay for the prostate: specific antigen utilizing two monoclonal antibodies. 170 85

Serum testosterone and prostate-specific antigen (PSA) levels were measured in 3 patients with Stage D2 prostate cancer before and after discontinuation of the long-acting LHRH agonist, goserelin acetate (Zoladex). The patients had received goserelin acetate for ten, sixteen, and thirty months prior to discontinuing the drug because of progressive metastatic disease. In all 3 patients, PSA and testosterone levels increased after goserelin acetate was discontinued. In 2 patients the testosterone level reached normal levels. A bilateral orchiectomy was performed one hundred sixty, one hundred, and seven days, respectively, after the drug was discontinued. In all 3 cases PSA and testosterone levels were reduced following castration, although PSA levels again began to increase within two weeks of orchiectomy in 2 of the 3 patients. These findings suggest that suppression of testosterone by LHRH agonists is not permanent and if tumor progression occurs, maintaining hormone suppression may still be beneficial.
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PMID:Response to orchiectomy following Zoladex therapy for metastatic prostate carcinoma. 170 66

Goserelin is a synthetic analogue of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); or gonadorelin] which stimulates gonadotrophin and sex hormone release in the short term, and then causes suppression with continued administration. Goserelin is given as a subcutaneous biodegradable depot incorporating 3.6 mg of the drug, which is released continuously at an average rate of 120 micrograms/day over 4 weeks. Monthly goserelin depot therapy produces partial disease remission or stabilisation in about 75% of men with previously untreated prostatic cancer, a rate equivalent to that achieved with orchidectomy or diethylstilbestrol (stilboestrol). The response to goserelin is more rapid than to diethylstilbestrol, and goserelin is better tolerated. About 30 to 45% of premenopausal women with breast cancer responded to goserelin using objective assessment criteria, suggesting comparability to ovariectomy. In benign hormone-dependent conditions, preoperative goserelin aids surgical removal of uterine leiomyoma (fibroids) and reduces blood loss, and 6 months of therapy relieves the signs and symptoms of endometriosis. The elevation in testosterone at the beginning of goserelin therapy can result in disease 'flare' in men with prostate cancer, and sex steroid suppression with continued treatment results in hot flushes and loss of libido in most patients. Thus, goserelin is an effective alternative to surgery or estrogen therapy in prostatic cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. Other gynaecological conditions reliant on the pituitary-gonadal axis also appear amenable to hormone manipulation with goserelin.
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PMID:Goserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical use in sex hormone-related conditions. 170 53

We report preliminary results for the first 164 patients enrolled in a multicenter study comparing the endocrine effects, efficacy, and safety of 3.6 mg of goserelin acetate (Zoladex) and orchiectomy in patients with Stage D2 prostate cancer. Eighty-one patients were randomly allocated to receive Zoladex and 83 to orchiectomy. The median follow-up time for all patients was two hundred ten days. Median serum levels of testosterone were reduced to castrate levels (less than 50 ng/dL) within four weeks in both groups and remained suppressed for up to sixty weeks. An objective response according to modified criteria of the National Prostatic Cancer Project was observed in 81 percent and 78 percent of patients in the Zoladex and orchiectomy groups, respectively. There were no statistically significant differences between treatment groups in the distributions of time to treatment failure or time to disease progression. The most commonly reported adverse events in both treatment groups were hot flashes, cancer-related pain, unspecified pain, and urinary symptoms. These results suggest that Zoladex may offer an alternative to orchiectomy in the treatment of advanced prostate cancer.
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PMID:Zoladex versus orchiectomy in treatment of advanced prostate cancer: a randomized trial. Zoladex Prostate Study Group. 182 32

The independent prognostic factors affecting survival were assessed in 240 men undergoing treatment for metastatic prostate cancer as part of a randomized clinical trial comparing the gonadotropin releasing hormone analogue Zoladex (goserelin acetate implant) with castration. In a multivariate analysis, the most highly significant predictors were the presence or absence of bone pain, serum testosterone levels, serum alkaline phosphatase levels, and performance status. Patients with all four factors favorable for survival had a 2-year survival rate of 84% as compared with only 8% for patients with none of the four factors favorable for survival. No other factors were significant. A separate analysis of serum testosterone levels revealed that the higher the pretreatment serum testosterone level, the greater the survival rate. Compared with patients with serum testosterone levels less than 6.9 nmol/L, significant differences in survival were observed for patients with serum testosterone levels of 10.4 to 13.9, 13.9 to 17.3, and over 17.3 nmol/L. These results have important implications for the design and analysis of future clinical trials of hormone therapy and for counseling patients regarding the short-term prognosis of their disease.
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PMID:Independent prognostic factors in patients with metastatic (stage D2) prostate cancer. The Zoladex Study Group. 203 35

Zoladex plus flutamide significantly delays the time to progression (subjective, objective, first progression) compared with orchiectomy, but no difference in survival (death from all causes or from malignant disease) could be detected. Thus, a delay in the appearance of progression has not improved survival. In fact, the duration of survival after progression tends to be shorter on Zoladex plus flutamide. There is thus no evidence to suggest any survival benefit with Zoladex plus flutamide. The quality control of our data revealed acknowledged problems in defining responses in patients with advanced prostate cancer. The review of the Bone Scan Committee provided the data for Tables 5 to 7. These data must provoke some reflections and emphasize once again the heterogeneity of the studied patient population. Table 4 on pain response after 4 weeks is just one of the many items to be analyzed by the committees for response criteria and quality of life. We expect that the other trials face similar problems. More work and patience are needed to obtain a firm answer to this clinical problem. These efforts will never be wasted, however, because the combined results of these trials will increase our knowledge of the treated history of prostate cancer and will, we hope, indicate a net treatment benefit in some subsets of patients. An individually tailored treatment for each patient selected from the anonymous mass of cases of advanced prostate cancer would be the highest reward of our continued collaboration with all the study groups.
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PMID:Total androgen ablation: European experience. The EORTC GU Group. 182 44


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