Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 28 untreated patients with asymptomatic, stage D prostate cancer was randomized in a double-blinded fashion to receive finasteride (10 mg. per day), a 5 alpha-reductase inhibitor or placebo. Patients were evaluated at 3-week intervals by rectal examination, and serum prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) levels, and at 6-week intervals by bone scan and transrectal ultrasound determinations of prostatic volume. Patients stopped the medication at week 6 at the discretion of the investigator when PSA levels increased from baseline. After 12 weeks all patients were reevaluated. Of the patients 13 received finasteride and 15 received placebo. The 2 groups did not differ statistically with respect to patient age, initial PSA and PAP level, or the extent of metastases on initial bone scan. A statistically significant decrease in the median percentage change from baseline in PSA at weeks 3 and 6 occurred in the finasteride group compared to the placebo group (-22.9% versus -2.9% and -15.1% versus +11.7%, respectively, p less than 0.05). Finasteride had no effect upon PAP, serum testosterone, prostatic volume or appearance of bone scans. A decrease in serum PSA in the finasteride treatment group suggests that finasteride exerts a minor effect in patients with prostate cancer. This effect does not approach that seen with medical or surgical castration yet because of the potency preserving feature and the lack of toxicity finasteride may warrant further study in the treatment of prostate cancer.
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PMID:Multicenter, randomized, double-blind, placebo controlled study to investigate the effect of finasteride (MK-906) on stage D prostate cancer. 138 74

The purpose of this work was to study the time sequence and the patterns of the multistep spread of metastases. Fifty-one patients with stage D carcinoma of the prostate, previously treated for their primary tumor by surgery or radiotherapy combined with hormonal manipulation and for metastases by hormones and chemotherapy, were included in the study. The metastatic dissemination, characterized primarily by the appearance of bone metastases, could follow two distinct patterns: The first, characterized by sequential appearance of osteoblastic metastases, followed by the development of osteolytic bone lesions, and the second pattern, characterized by the simultaneous appearance of osteoblastic and osteolytic bone lesions. In cases with solely osteoblastic bone metastases, the lesions are hormone sensitive and long-lasting remissions could be obtained. The development of osteolytic bone lesions is usually accompanied by the recurrence of the primary tumor and appearance of metastases in other sites, such as the lymph nodes and lungs. Bone metastases became resistant to hormonal manipulation and with chemotherapy short remissions were obtained. The course of the terminal period is faster, with shorter survival times. The determination of serum acid and alkaline phosphatase levels seems to reflect the course of the disease during the initial period of the disease only, i.e. when bone metastases are sensitive to hormonal treatment.
Clin Exp Metastasis
PMID:The course of metastatic disease originating from carcinoma of the prostate. 404 59

Radiotherapy often is used for palliation of bone pain from metastatic cancer of the prostate but an objective evaluation of its efficacy in a large series of patients is unavailable. We report the results of external beam irradiation in 62 patients who had bone pain secondary to stage D carcinoma of the prostate. The variables used to judge pain before and after radiotherapy included subjective evaluation of pain, status of activity and quantitation of analgesic use. Complete relief of pain was achieved in 26 patients (42 per cent), partial relief in 22 (35 per cent) and no relief in 14 (23 per cent). On the basis of our experience external beam irradiation is useful palliative therapy for pain from metastatic cancer of the prostate.
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PMID:External beam radiotherapy for palliation of pain from metastatic carcinoma of the prostate. 617 95

Adenocarcinoma of the prostate is the most common malignant neoplasm occurring in men. About half of patients present with metastatic disease. The mainstay of the treatment of stage D cancer of the prostate is hormonal therapy. Bilateral simple orchiectomy remains the gold standard with which other therapies must be compared. Luteinizing hormone-releasing hormone analogues and antiandrogens are now most commonly used but are costly. Initiating hormonal therapy immediately on diagnosing metastatic disease appears to have some advantage over delaying therapy until a patient is symptomatic. Total androgen blockade also appears to be beneficial in terms of survival but at high cost.
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PMID:Hormonal therapy for stage D cancer of the prostate. 802 85

Surgical orchidectomy is a simple procedure with few physical side effects, low mortality, and cost effectiveness. Nevertheless, there can be negative sequelae such as sexual dysfunction, impaired quality of life, and poor body image. Although it is a frequent treatment approach for prostate cancer, it is not clear whether these sequelae are problematic for this patient group. It is possible that relief from painful metastases and the prolongation of life outweigh these negative factors. The present study investigated quality of life, sex-role identity, and sexual function in 15 patients with stage D prostate cancer, before and after surgery. Orchidectomy did not appear to affect quality of life, or sex-role identity. However, loss of sexual function did present as an area of concern. It was noted that 55% of premorbidly sexually active patients found this loss disturbing. These patients, premorbidly, appeared to have higher sex-role stereotypy.
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PMID:Quality of life, sexual functioning and sex role identity after surgical orchidectomy in patients with prostatic cancer. 871 69

In this report, we describe a method for quantitative bone scan interpretation (the Bone Scan Index or BSI) in advanced prostate cancer. The BSI estimates the fraction of the skeleton that is involved by tumor, as well as the regional distribution of the metastases in the bones. The purpose of this report is to describe the development and validation of this method in terms of reproducibility and the application of BSI for determining extent of disease and monitoring disease progression. We analyzed 263 bone scans from 90 patients being studied under four protocols at Memorial Sloan-Kettering Cancer Center for progressive, androgen-independent prostate cancer (AIPC), who had bone scans as a part of their work-up. We determined: (a) the intraobserver and interobserver variability of the BSI; (b) the comparison between a change in BSI and prostate-specific antigen (PSA); (c) the regional distribution of bony metastases in early stage D prostate cancer (<3% skeletal involvement); and (d) the rate of growth of bony metastases from prostate cancer. A cube root transformation of the percentage of involvement of the entire skeleton was used to stabilize the variance over the entire span of values (0-60% tumor involvement). The range of interobserver variability between readers was 0.2-0.5 times the cube root of the BSI (69 scans, 18 patients). Intraobserver variability was minimal when the same reader read the same scans after a 2-year interval, showing a correlation coefficient of 0.97 (reader 1) and 0.99 (reader 2), P < 0.001. There was a parallel rise in the BSI and the PSA in 24 patients (105 scans) treated for AIPC with hydrocortisone followed by suramin at PSA relapse (Pearson's moment correlation, 0.71). In a group of 27 patients with limited bone involvement by AIPC (i.e., <3% BSI), the distribution of early metastases was not random within the skeleton but was distributed in the central skeleton in a manner that matched the distribution of the normal adult bone marrow. Also, in a group of 21 patients (62 scans), the change in BSI as a function of time after diagnosis was explored graphically. The progression of bone scan changes in AIPC, from early involvement (<3%) to late involvement, was fitted to a Gompertzian equation. It showed a rapid exponential growth phase, with an estimated tumor doubling time of 43 days when the BSI was 3.3%. The change in BSI rapidly approached a more gradual slope as the percentage of skeletal involvement increased. The BSI provides a reproducible new parameter for quantitative assessment of bone involvement by AIPC. These results suggest that the BSI will be useful for stratifying patients entering treatment protocols for extent of tumor involvement of bone. Although further study is necessary, serial bone scan BSI appears capable of quantifying both the progression of bony involvement by tumor as well as the response to treatment.
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PMID:A new parameter for measuring metastatic bone involvement by prostate cancer: the Bone Scan Index. 967 53

Prostate cancer represents one of the most important health problems in industrialized countries. It is the second leading cause of cancer-related death in the United States. Therapeutic options are different according to the stage of the disease at the diagnosis. Patients with localized disease may be treated with surgery or radiation, whereas the treatment for patients with a metastatic disease is purely palliative. Hormonal treatment represents the standard therapy for stage IV prostate cancer, but patients ultimately become unresponsive to androgen ablation and are classified as hormone-refractory prostate cancer patients. The molecular mechanisms involved in progression in hormone resistance are characterized by mutations, down and up-regulation in the androgen receptor gene, mutations in p53 and over-expression of Bcl2 and other alterations in genes and in gene expression. The important thing is that we understand these mechanisms to define potential therapeutic agents for the treatment of hormone-refractory prostate cancer patients. Conventional options for patients with hormone-refractory prostate cancer include secondary hormone therapy, radiotherapy and cytotoxic chemotherapy. The commonest antineoplastic agents are mitoxantrone, estramustine and taxanes. Despite an improvement in the palliative benefit, none of these agents has demonstrated a beneficial impact on the overall survival of patients. Therefore, there is no standard therapy for these patients, thus we need new approaches which should be studied in clinical trials. The evaluation and incorporation of new agents into current treatment regimens could have a role in the treatment of hormone-refractory prostate cancer, but their efficacy has not yet been demonstrated.
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PMID:Treatment options in hormone-refractory metastatic prostate carcinoma. 1576 53

The enhanced permeability and retention (EPR) effect, a tumor-targeting principle of nanomedicine, serves as a standard for tumor-targeted anticancer drug design. There are 3 key issues in ideal EPR-based antitumor drug design: i) stability in blood circulation; ii) tumor-selective accumulation (EPR effect) and efficient release of the active anticancer moiety in tumor tissues; and iii) the active uptake of the active drug into tumor cells. Using these principles, we developed N-(2- hydroxypropyl)methacrylamide (HPMA) copolymer-conjugated pirarubicin (P-THP), which uses hydrazone bond linkage; it was shown to exhibit prolonged circulation time, thereby resulting in good tumor-selective accumulation. More importantly, the hydrazone bond ensured selective and rapid release of the active drug, pirarubicin (THP), in acidic tumor environments. Further, compared to other anthracycline anticancer drugs (eg, doxorubicin), THP demonstrated more rapid intracellular uptake. Consequently, P-THP showed remarkable antitumor effect with minimal side effects. In a clinical pilot study of a stage IV prostate cancer patient with multiple metastases in the lung and bone, P-THP (50-75 mg administered once every 2-3 weeks) was shown to clear the metastatic nodules in the lung almost completely after 3 treatments where 50-70 mg THP equivalent each was administerd per 70 kg body wt, and bone metastasis disappeared after 6 months. There was no recurrence after 2 years. The patient also retained an excellent quality of life during the treatment without any apparent side effects. Thus, we propose the clinical development of P-THP as an EPR-based tumor-targeted anticancer drug.
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PMID:[Missile-Type Tumor-Targeting Polymer Drug, P-THP, Seeks Tumors via Three Different Steps Based on the EPR Effect]. 2721 83