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)

Hormone-refractory prostate cancer is an advanced stage of the metastatic disease; it has a poor prognosis and a short median survival, about 9 to 18 months. The current article is based on a literature review regarding the prognostic factors and medical treatments, with a focus on recent advances in chemotherapy. With the use of docetaxel that increases the median survival of this disease and improves the symptoms, new clinical protocols have been developed, with promising results; these protocols propose a combination with calcitriol or antiangiogenic agents. Supportive care is also an important part of the treatment due to the high level of bone involvement and its consequences. Such recent advances constitute a real progress in the management of prostate cancer, namely the pharmacological combinations with a promising efficacy and little toxicity.
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PMID:[Hormone-refractory prostate cancer]. 1748 12

The aim is to evaluate the efficacy and toxicity of weekly docetaxel and estramustine for Japanese men with hormone refractory prostate cancer who were treated at a single institution. Twenty eligible patients had histologically proven adenocarcinoma of the prostate with metastases that were progressing despite complete androgen blockade and antiandrogen withdrawal. All of the patients received docetaxel 30 mg/m(2) weekly (days 1, 8, 15, 22, 29, and 36). After a two week break, the treatment schedule was repeated. Patients were scheduled to receive daily oral estramustine 560 mg/day throughout the protocol. In the serum prostate specific antigen (PSA) response, three (15%) patients achieved a complete response, and 8 (40%) acheived a partial response. Overall survival and time to progression were 13.4 months and 6.4 months, respectively, however sixty-seven percent of the patients had to discontinue treatment because of toxicity. The high toxicity of this protocol suggests that the regimen and/or the timing should be altered for Japanese patients.
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PMID:Combination chemotherapy with weekly docetaxel and estramustine for hormone refractory prostate cancer in Japanese patients. 1818 88

Advanced prostate cancer with skeletal metastases entails significant symptoms from both treatment and the disease itself. Although the diagnosis is a common one, knowledge of the symptom experience late in the disease trajectory is limited. The aim of the present study was to describe the experience of physical symptoms in men with hormone refractory prostate cancer and skeletal metastases. Twenty men answered a quality of life questionnaire before participating in semi-structured interviews. The interviews were analyzed using qualitative description. Findings show that the dominant symptoms were lack of energy and pain. Interestingly when talking about lacking energy the men described three different variants; lack of mental energy or initiative, lack of strength and stamina, and tiredness or sleepiness. Also, three different types of pain were described; pain from skeletal metastases, a diffuse moving pain, and pain not directly caused by the prostate cancer. Though a majority of the men scored being dissatisfied with their sex life; in the interviews, this was not described as a major distress. The findings also showed that the men experienced different symptoms despite the same diagnosis, skeletal metastases, stage, and androgen deprivation treatment, and that these symptoms are not necessarily experienced as problems or causing distress.
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PMID:Experiences of symptoms in men with hormone refractory prostate cancer and skeletal metastases. 1844 Aug 62

The aim of the present study was to compare a novel marker for high bone turnover with two routine markers for screening in prostate cancer patients. The markers were evaluated in two studies: (a) a cross-sectional study of 170 prostate cancer patients with local disease stratified by +/-lymph node metastases (N 0, N1) compared with controls and (b) a longitudinal study of 40 hormone refractory prostate cancer patients stratified by skeletal involvement and followed during docetaxel (+/-BM) and zoledronate (+BM) treatment. Presence or absence of bone metastases (BM) was assessed by imaging techniques (magnetic resonance imaging or X-ray) and technetium-99m scintigraphy. The serum or urinary levels of alpha C-telopeptide of collagen type I (alphaalphaCTX), prostate-specific antigen (PSA), and total alkaline phosphatase (tALP) were assessed. PSA was elevated in both N 0 and N1 patients compared with controls, whereas alphaalphaCTX was elevated only in N1 patients. tALP exhibited no difference in any of the groups. In the treatment study, PSA decreased with treatment in both the -BM and +BM groups compared with baseline values, showing similar effect of docetaxel or docetaxel/zoledronate treatment on this marker. On the contrary, alphaalphaCTX and tALP did not decrease with docetaxel treatment in the -BM group compared with baseline, whereas it decreased significantly with docetaxel/zoledronate treatment in the +BM group, already after 1 month of treatment for alphaalphaCTX. Results suggest that alphaalphaCTX is superior to PSA and tALP for identifying patients having a high risk of metastatic disease and for monitoring skeletal progression in +BM prostate cancer patients during treatment.
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PMID:Biochemical markers for monitoring response to therapy: evidence for higher bone specificity by a novel marker compared with routine markers. 1848 50

The disease trajectory of living with incurable cancer is characterized by increasing bodily deterioration and problems. In this paper, we have focused on the change in temporal awareness as manifested in the narrations of two men with hormone refractory prostate cancer and skeletal metastases as they approach death. The two men participated in in-depth research interviews during the last part of their lives, sharing a similar disease trajectory with increasing bodily change and decreasing physical function. Both died a lingering, cancer-related death. The first and last research interviews were analyzed using a discourse analytic method. Findings show that the temporal awareness in the interviews changes as the illness progresses and death approaches. In the last interviews, the present is flooded with bodily problems; the past and the future are hardly present except for the future beyond the men's own deaths. Pain, fatigue, nausea, and other symptoms figure largely in this change, and there is no time for much more than attending to bodily needs in a present that is dominated by problems. Here, the importance of alleviating bodily problems once again becomes paramount, and two questions are raised: Is the often reported withdrawal from life, when death is imminent, a physical necessity rather than a psychological one, and is it possible to free time from the time-consuming problems of the present by means of a more concentrated attempt to alleviate these problems?
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PMID:Time and bodily changes in advanced prostate cancer: talk about time as death approaches. 1850 95

Metastases from prostate cancer occur largely in bone through a haematogenous route. Metastatic spread of prostate cancer to the leptomeninges was rarely seen in the past. However, there has been a recent increase in presentations of leptomeningeal spread from prostate cancer in our institutions. Between 2004 and 2006, four patients were diagnosed with metastatic prostate cancer with leptomeningeal metastases in our centres. All four patients had hormone refractory prostate cancer and had previously had chemotherapy. The median survival of these patients was approximately 15 months from the time of hormone refractoriness. The prognosis of leptomeningeal metastasis secondary to metastatic prostate cancer is poor, ranging from 2 to 7 months as seen in our series. New cases of leptomeningeal metastases seen in our series are hypothesized to be secondary to the use of effective modern systemic treatments. A parallel might be drawn with the increased rate of central nervous system metastases in breast cancer since the introduction of effective cytotoxic treatments and more recently targeted therapies. We suggest the clinicians to be aware of the potential change of natural history and pattern of progression in metastatic prostate cancer.
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PMID:Increased detections of leptomeningeal presentations in men with hormone refractory prostate cancer: an effect of improved systemic therapy? 1881 63

Members of the gastrin-releasing peptide (GRP) family and its analogs bombesin (BBN) have been implicated in the biology of several human cancers including prostate, breast, colon and lung. To date, three mammalian GRP/BBN receptor subtypes have been cloned and characterized: the neuromedin B receptor (NMBR), the GRP receptor (GRPR) and the BBN-receptor subtype 3 (BB(3)). The fourth BBN receptor subtype, BB(4), has only been identified in amphibian and at present no mammalian equivalent of this receptor has been described. GRPR analogs have been used as carriers to deliver drugs, radionuclides and cytotoxins to target various cancer types that are GRPR positive. We investigated the in vitro binding properties of (177)Lu-AMBA, a novel radiolabelled BBN analog currently undergoing clinical trial as systemic radiotherapy for hormone refractory prostate cancer (HRPC) patients. Pharmacological analyses of the (177)Lu-AMBA was determined using in vitro binding studies using membrane target system containing specific receptor subtypes. We investigated the distribution of binding sites for (177)Lu-AMBA by receptor autoradiography on human neoplastic and non-neoplastic tissues. Pharmacological characterizations of (177)Lu-AMBA shows, high affinity towards NMB and GRP receptors, while little or no affinity towards BB(3) receptor. Among the 40 different types of non-neoplastic tissues tested seven of them showed limited but specific binding of (177)Lu-AMBA. Fourteen of 17 primary prostate cancers, six of 13 primary breast cancers expressed binding sites for (177)Lu-AMBA. Furthermore, no apparent differences in (177)Lu-AMBA-binding sites expression were observed between matched pairs (primary vs. secondary) of prostate and breast cancer tissues. These data represent the molecular basis for clinical applications of (177)Lu-AMBA for diagnosis and treatment of GRP-R and NMB-R positive tumors.
Clin Exp Metastasis 2009
PMID:In vitro binding evaluation of 177Lu-AMBA, a novel 177Lu-labeled GRP-R agonist for systemic radiotherapy in human tissues. 1897 17

Since 2004 and the first improvement in overall survival in hormone refractory prostate cancer patients (HRPC) brought about by docetaxel, numerous phase II and III studies have been initiated. Considering the lack of efficacy in terms of overall survival, hormonal manipulations such as antiandrogen withdrawal, di-ethylstilbesterol or dexamethason are only indicated in "rising PSA" patients without clinical or radiological evidence of metastases. As first line treatment, the optimal chemotherapy regimen is docetaxel (75 mg/m(2) every 3 weeks) in association with prednisone (5 mg twice daily). Second line chemotherapies (mitoxantron, ixabepilon, docetaxel as a re-treatment, vinorelbin, doxorubicin...) provide modest results only in terms of progression-free survival. A phase III study of Straplatin has been prematurely interrupted. Targeted anti-angiogenic therapies have shown encouraging results in patients with metastatic localizations, and underline the need to identify target patients early through cellular markers (mTOR or EGFR overexpression) as well as the uselessness of PSA dosage to monitor efficacy. An ongoing phase III study is evaluating bevacizumab in association with docetaxel to improve overall survival. Both the Provenge vaccine and DN 101 (calcitriol) showed a survival gain of a few months in phase III studies. An ongoing EORTC phase II trial is evaluating antisense oligonucleotids in HRPC. Early introduction of docetaxel raises the issue of when to start chemotherapy as it may be relevant to initiate this treatment before the onset of hormone independence. GETUG 15 trial will try to answer this question.
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PMID:[Chemotherapy of hormonorefractory and hormonoresistant metastatic prostate cancer]. 1907 Aug 17

We report the case of a patient with metastatic hormone refractory prostate cancer in whom "indirect" cauda equina syndrome developed concurrent with multilevel spinal cord compression (SCC). Three months after his first positive bone scan, a 65-year-old otherwise healthy man presented with severe back pain, bilateral lower extremity paresthesias, leg weakness and urinary retention. Magnetic resonance imaging (MRI) showed a dural-based mass causing SCC at the T9, T10 and T11 vertebrae, with a normal cauda equina. He received corticosteroids and palliative external beam radiotherapy, resulting in good pain control and gradual improvement in his neurological symptoms. He did well for 8 months, at which time his residual bilateral leg weakness abruptly worsened and he experienced numbness, paresthesias, urinary incontinence and constipation. Repeat MRI showed progression of epidural metastatic disease compressing the spinal cord or thecal sac at 7 thoracic vertebral levels. The cauda equina was also distorted and flattened without evidence of direct solid tumour impingement. We hypothesized that the etiology was increased intrathecal pressure due to disrupted cerebrospinal fluid flow resulting from multiple levels of upstream thecal sac compression. It is essential to image the entire spinal cord and cauda equina when patients with metastatic bone disease present with neurological symptoms to institute correct treatment and preserve function and mobility.
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PMID:A case of indirect cauda equina syndrome from metastatic prostate cancer. 1967 34


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