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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgen ablation using hormonal manipulation is used extensively in metastatic prostate cancer; however, its use in localized disease combined with surgical extirpation of the gland has not been thoroughly and systematically investigated. The rationale for neoadjuvant therapy stems from the demonstrated effectiveness of androgen ablative therapy in metastatic disease and the high rate of "positive" surgical margins, especially in patients with Stage B2 disease. In addition, the essentially anecdotal clinical report of Scott and Boyd [1], using endocrine therapy plus radical prostatectomy in patients with Stage C disease, gives 15 year survival results comparable to those obtained by Jewett [2] in Stage 1 patients treated by radical prostatectomy. Finally, experimental observations in the androgen-sensitive mammary tumor (Shionogi) lend support to the concept of neoadjuvant hormonal manipulation. A pilot study of neoadjuvant endocrine therapy in 55 patients treated at Memorial Sloan-Kettering Cancer Center with 3 months of diethylstilbestrol (DES) (3 mg/day) prior to radical prostatectomy indicates marked reductions in prostate-specific antigen (PSA), although persistent evidence of adverse local tumor features was common. Some patients, however, exhibited evidence of significant downstaging. Whether or not any alteration in disease progression will accrue from demonstrated local downstaging is, of course, uncertain. However, clinical and laboratory effects of such treatment may provide a means for correlation with subsequent tumor behavior, and may prove useful in treatment decisions. Additionally, a decrease in the number of foci of grade 3 prostatic intraepithelial neoplasia (PIN-3) was noted in a small number of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neoadjuvant hormonal manipulation: a strategy for chemoprevention trials. 128 66

The best treatment for adenocarcinoma of the prostate depends on the patient's age, general medical condition, life expectancy, and willingness to accept such side effects as impotence. Radical prostatectomy or full-dose radiation therapy are usually curative when cancer is confined to the gland. The technique of prostatectomy has been improved and potency often can be preserved. Once the tumor extends beyond the gland, treatment alternatives are radiation or endocrine therapy. If lymph nodes are negative, radiation therapy may result in a long period without progression. If lymph nodes are positive, the expense and morbidity of radiation therapy may not be worthwhile because the likelihood of cure is low. Androgen deprivation, or endocrine manipulation, is preferred for metastatic disease. Response is varied and may depend on the patient's testosterone level when therapy is initiated. Survival is shorter in those with levels below normal.
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PMID:Adenocarcinoma of the prostate. Stage-by-stage treatment alternatives. 305 50

In 100 patients with trophoblastic tumors the functional activity of the adrenal cortex was examined before and after chemotherapy. Androgen-producing function of the adrenal cortex was found to be reduced as well as the absolute number of excreted 17-ketosteroids separate fractions and their ratio. The glucocorticoid function of the adrenal cortex shows a monotonous character. Only in patients having uterine chorion-epithelioma with metastases a reliable reduction of the fraction of 11-hydroxy-17-ketosteroids is noted before and after chemotherapy, while the per cent content of free 17-oxy-corticoid fraction is increased with regard to their total amount. Successful chemotherapy, associated with a lower titre of chorionic gonadotropins up to its complete disappearance, does not result in normalization of values characterizing the functional activity of the adrenal cortex.
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PMID:[Adrenal cortex function in trophoblastic disease]. 625 71

Androgen deprivation therapy is the initial treatment choice for metastatic disease. When enrolling patients into androgen deprivation trials, it is important to consider stratification of enrollees based on prognostic factors that have been identified as important in determining the likelihood of response. Prognostic factors are also helpful in identifying which patients are less likely to respond to treatment; this information also would help to counsel patients. Performance status is an important prognostic factor; however, its impact is minimal because the great majority of men who receive treatment for advanced disease have a normal performance status. Hemoglobin, alkaline phosphatase, and a semiquantitative grading scale for the number of metastatic foci on the bone scan are useful prognostic factors. The pretreatment serum testosterone level is a powerful prognostic factor. Patients with a low serum testosterone level have a shorter progression-free survival than men whose pretreatment serum testosterone level is above normal. The prognostic importance of pretreatment serum testosterone level has been evaluated in studies using treatment methods that lower this level to castrate levels. Recently, we found that serum testosterone level was not a prognostic factor for men taking the nonsteroidal antiandrogen, Casodex (Zeneca, Wilmington, DE), which does not alter the serum testosterone level. The pretreatment serum prostatic-specific antigen also is a prognostic factor. This antigen may be the best single method for monitoring patients in regard to response to or progression following therapy. The return of the prostatic-specific antigen level to normal (< 4 ng/ml), or the decline in the prostatic-specific antigen level of > 90% indicates a prolonged progression-free survival. In the future, it will be interesting to incorporate both the initial prognostic factors as well as monitor the prostatic-specific antigen into a multivariate analysis, which will be highly predictive of a man's response to treatment.
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PMID:Prognostic factors in metastatic prostate cancer. 750 77

Prostate cancer is a disease of older men, with more than 80% of cases being diagnosed in men 65 years of age and older. Broader participation in screening and early detection programs has resulted in many diagnoses being made earlier in the course of the disease. However, an estimated 25-30% of cases among older men will be diagnosed as metastatic disease. These will be men initially diagnosed with metastatic disease as well as men previously treated for localized disease that has progressed to metastatic disease. The treatment of metastatic prostate cancer has been straightforward. Objective prognostic factors are assessed, and recommendations for the most suitable hormonal therapy are made. Androgen withdrawal, androgen blockade, or combination therapy are current first-line treatment modalities. Patients with good prognostic factors will generally do well for a long time, even experiencing a time-limited remission. Patients with a poor prognosis will die of their disease, with median survival being 18 months. Pretreatment assessment of men diagnosed with metastatic prostate cancer should include prognostic factors (tumor volume, histologic grade, DNA ploidy, and prostate specific antigen), health status (comorbidity and performance status), quality of life factors (as a baseline against which to evaluate subjective response and to predict subjective progression), and psychosocial dimensions (sexuality and sexual function, self image, sociability, and social support). Each of these assessment areas will provide important predictors for suitable treatment, response and progression, and survival. The challenge presented is the time and difficulty involved in weighing all these areas and in making an informed physician-patient decision on the most appropriate treatment plan. The physician must direct a health care team to treat metastatic prostate cancer effectively. This team includes oncology nurses, dietitians, social workers, spouses, significant others, and the patient himself.
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PMID:Pretreatment of metastatic disease. Prostate cancer in the older male. 808 88

Androgen ablation therapy is the treatment of choice for the palliation of patients with advanced prostate cancer. In addition to palliation, maximal androgen ablation (MAA), with a combination of medical or surgical castration and an antiandrogen, has been shown to increase the survival of patients with metastatic prostate cancer in at least three large well-conducted trials. A subgroup analysis of these trials has suggested that patients, particularly those with low volumes of metastatic disease, fared much better when treated with MAA than with castration alone. This observation has prompted many clinicians to begin androgen ablation earlier in men with advanced but not necessarily metastatic prostate cancer, thus exposing them to prolonged periods of androgen ablation and its side effects. These include impotence, loss of libido, loss of muscle mass, malaise, and psychological disturbances. In order to offer the putative advantages of early hormone therapy but to mitigate its side effects a number of innovative methods of androgen ablation are under investigation. These include 'sequential androgen blockade' and 'intermittent androgen suppression'. Sequential androgen blockade uses a 5 alpha-reductase inhibitor to reduce the conversion of testosterone to dihydrotestosterone in conjunction with an antiandrogen or androgen-receptor blocker to prevent residual androgen from reaching the androgen receptor. Circulating testosterone levels are not reduced thus minimizing side effects. Intermittent androgen suppression uses combined therapy to rapidly reduce serum testosterone and induce tumor regression. From time to time treatment is stopped and androgen concentrations rise. This method reduces the total time of exposure to castrate levels of androgen and, although prostate-specific antigen levels rise during the second phase of therapy suggesting tumor growth, proponents of this cycling method suggest that this should prolong the time to androgen independence of the tumor. Early results with both methods suggest that the time to progression is long and side effects are minimized as compared to MAA. Large scale trials will be needed to determine the exact risks and benefits of these novel methods of androgen ablation.
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PMID:Innovative approaches to the hormonal treatment of advanced prostate cancer. 926 90

Our laboratory has developed two cellular models of human prostate cancer progression. The LNCaP prostate cancer progression model is based upon the well-known cellular interaction between human prostate or bone stromal cells and LNCaP cells in vivo. The marginally tumorigenic LNCaP cells acquired tumorigenic and metastatic potential upon cellular interaction with either prostate or bone fibroblasts. A subline termed C4-2 was observed to grow readily in castrated animals and acquired metastatic potential spreading from the primary tumor site to the lymph node, the seminal vesicles, and the axial skeleton, resulting in an intense osteoblastic reaction. The second model is ARCaP, where prostate cancer cells derived from the ascites fluid of a man with metastatic disease exhibited an Androgen- and estrogen-Repressed Prostate Cancer cell growth and tumor formation in either a hormone-deficient or a castrated environment. However, the growth of either the tumor cells in vitro or the tumors in vivo was suppressed by both estrogen and androgen. While the tumor cells expressed low levels of androgen receptor and prostate-specific antigen (PSA), they were highly metastatic when inoculated orthotopically. Distant metastases to a number of organs were detected, including the liver, lung, kidney, and bone. We have employed a human prostate cancer progression model as a system to study the efficacy of gene therapy. Results of the study show that whereas universal promoters, such as Cytomegalovirus (CMV) and Rous Sarcoma Virus (RSV) promoter-driven tumor suppressors (e.g. p53, p21, and p16), were effective in inhibiting prostate tumor growth, the advantages of driving the expression of therapeutic toxic genes using a tissue-specific promoter prostate-specific antigen (PSA) and a tumor--but not tissue-specific promoter, osteocalcin (OC), are preferred. In the case of the PSA promoter, we can achieve cell-kill in PSA-producing human prostate cancer cells. To circumvent the supporting role of bone stroma for prostate cancer epithelial growth, we have recently developed a novel concept where the expression of therapeutic toxic genes is driven by a tumor--but not a tissue-specific OC promoter. Osteocalcin-thymidine kinase (OC-TK) was found to efficiently eradicate the growth of osteosarcoma, prostate, and brain tumors both in vitro and in vivo. We observed that androgen-independent human prostate cancer cells lines expressed OC-TK at higher levels than androgen-dependent human prostate cancer cell lines. We have obtained data to suggest that Ad-OC-TK plus a pro-drug acyclovir (ACV) may be used as an effective therapy to treat prostate cancer bone metastasis in models where the growth of androgen-independent PC-3 and C4-2 tumors in the bone has occurred.
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PMID:Human prostate cancer progression models and therapeutic intervention. 943 28

Radiotherapy is an effective treatment for localized prostate cancer. A dose response relationship has been demonstrated for both local tumor control and complications. Reducing the volume of normal tissue treated may allow dose escalation without an increase in RT induced side effects. Androgen blockade before RT could, by reducing tumor volume, increase local control, disease-free (DFS) and overall survival in patients (pts) with prostatic adenocarcinoma. A total of 79 patients with T2-T4 prostate cancer have been treated initially with LHRH agonists and cyproterone acetate followed by radical irradiation between 1988 and 1993. The first cohort of 22 patients were monitored intensively by transrectal ultrasound and computed tomography. For each patient conformal photon beam radiotherapy and conventional treatment plans were produced and dose volume histograms compared for total volume, rectal volume, and bladder volume. Overall mean reduction of prostate volume was about 50%, and radiotherapy target volume was reduced by 37%. 53 further patients without clinical evidence of regional or distant metastases were given 3 months preradiotherapeutic hormonal cytoreduction with a short course of cyproterone acetate and LHRH. PSA level fell rapidly in most patients and after 3 months treatment the median PSA level was 1 ng/ml and 83% had PSA level 10 ng/ml. At 18 months PSA levels continued to be < 2 ng/ml in 70% of the patients. Combined modality treatment with the neoadjuvant or adjuvant androgen deprivation and conformal therapy show considerable promise as novel methods to improve the therapeutic ratio. This treatment approach may be used to explore the possibility of dose escalation in prostate cancer to enhance local control, and therapeutic randomised studies are underway to test these approaches.
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PMID:[Basic principles and initial results of adjuvant hormone therapy and irradiation of prostatic carcinoma]. 948 May 9

Androgen blockade is the mainstay of therapy in the clinical management of advanced prostate cancer. Recent progress on two fronts--the development of newer xenograft and transgenic models and a greater understanding of nuclear receptor signaling--has provided new insight into mechanisms of androgen-dependence in prostate cancer. This review centers on the concept that perturbations in androgen receptor signaling are likely to occur early in prostate cancer and play a critical role in progression to end stage hormone-refractory disease.
Cancer Metastasis Rev
PMID:Mechanistic concepts in androgen-dependence of prostate cancer. 1045 86

Prostate adenocarcinoma is the most common nonskin malignancy in males and the second most common cause of cancer death in the United States (Landis et al., 1998). Initial treatments of surgery or radiotherapy may cause impotence and/or incontinence from neural damage (Eastham and Scardino, 1998; Porter et al., 1998). When extraprostatic or metastatic disease develops, castration or pharmaceutical androgen ablation is utilized (Catalona, 1994). Androgen-resistant recurrence indicates a poor prognosis and justifies experimental chemotherapy (Oh and Kantoff, 1998). G207 (Mineta et al., 1995; Yazaki et al., 1995) is a multimutated herpes simplex virus 1 (HSV) vector that replicates within cancer cells, causing cellular death; however, replication is limited in normal cells, including those of the nervous system. In vitro, G207 at a low multiplicity of infection (MOI of 0.01) is oncolytic for multiple human prostate cancer cells. In athymic mice, a single intraneoplastic inoculation of G207 completely eradicates >22% of established subcutaneous human prostate cancer tumors irrespective of hormonal responsiveness. Two intraneoplastic inoculations of G207 completely eradicated two of three recurrent previously irradiated tumors and two intravenous administration of G207 induced tumor regression in distant subcutaneous tumors and completely eradicated one-fourth of the tumors.
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PMID:Local and systemic therapy of human prostate adenocarcinoma with the conditionally replicating herpes simplex virus vector G207. 1049 54


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