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)

The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases.
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PMID:[Treatment strategy for advanced prostate cancer with bone metastases]. 1691 23

Examination of 127 patients with generalized prostate cancer established a low prophylactic effect of systematic treatment with strontium-39 chloride: it failed to alleviate pain in metastatic cancer, nor was it followed by longer mean survival. Repeat systematic radiotherapy is not indicated when palliative measures such as hormonal therapy, local radiotherapy and chemotherapy are still effective.
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PMID:[Effectiveness of repeated systematic radiotherapy for generalized prostate cancer]. 1703 36

Cancer metastasis to the bone develops commonly in patients with a variety of malignancies, and is a major cause of morbidity and diminished quality of life in a significant proportion of cancer patients. The effective treatment of bone metastasis requires cooperation between medical, surgical and radiation oncologists. Radiotherapy, either in the form of targeted external beam radiation therapy, or systemic administration of radionuclides, plays a central role in treatment of symptomatic bone metastases. The appropriate external beam treatment techniques, dose and fractionation regimens for the treatment of symptomatic, localized bone metastasis have been established in prospective clinical trials. Large-field, hemi-body irradiation has been utilized for treatment of symptoms related to more widely disseminated bone metastases, but has been associated with substantial toxicity. Strontium-89 and Samarium-153 are widely available systemically administered radionuclides that are useful for the treatment of widely disseminated disease, and have largely supplanted the use of hemi-body irradiation. Combined with appropriate medical and surgical interventions, as well as the appropriate use of analgesics, radiotherapy is a well-tolerated and highly effective treatment for the palliation of symptomatic bone metastases.
Cancer Metastasis Rev 2006 Dec
PMID:Targeted and systemic radiotherapy in the treatment of bone metastasis. 1716 May 56

Nuclear medicine techniques continue to be important non-invasive imaging tools assisting the diagnosis, monitoring and--in some cases--treatment of prostate cancer. Bone scintigraphy was the premier modality to have an extensive role in the staging of prostate cancer and has remained an integral tool for over three decades in the assessment of newly diagnosed disease or in follow-up staging. Therapeutic treatment and palliation of disseminated disease, particularly in the skeleton, has also been successful with several radioisotopes including strontium-89 chloride. Despite advances in nuclear medicine techniques and molecular imaging technology such as positron emission tomography and radioimmunoscintigraphy, bone scintigraphy still remains the gold standard in the assessment of osseous metastatic disease in prostate cancer. Thus, it is important to continually review the modalities that have remained important over time and not just to focus on newer technologies. This article summarizes the current diagnostic and therapeutic use of radioisotopes for bony disease in prostate cancer with particular reference to radionuclide bone scintigraphy and positron emission tomography.
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PMID:Diagnostic and therapeutic use of radioisotopes for bony disease in prostate cancer: current practice. 1730 62

Many patients with cancer develop symptomatic skeletal metastases at an advanced stage of their disease. Skeletal metastases are often complicated by pain. They cause considerable morbidity and mortality. Besides analgesics, treatment options include external beam radiotherapy, bisphosphonates, chemotherapy, surgery and bone seeking radiopharmaceuticals. Pain palliation with bone seeking radiopharmaceuticals has proved to be an effective treatment modality in patients with metastatic bone pain. Radiopharmaceuticals bind to the bone matrix in areas of increased bone turnover, due to a metastatic response. Beta rays from the specific radionuclide, bound to its carrier ligand, result in the therapeutic effect. Various radiopharmaceuticals have been developed for this purpose. All have their own characteristics. The radiopharmaceuticals Samarium-153-ethylenediaminetetramethylenephosphonic acid ((153)Sm-EDTMP) and Strontium-89-Chloride, which are approved in the USA and Europe, as well as the not universally approved Rhenium-186-hydroxyethylidenediphosphonic acid ((186)Re-HEDP), will be discussed in greater detail. Depending on the half-life and radiation energy of the specific radionuclide, they exert a different effect and toxicity profile. In most cases, bone marrow toxicity is limited and reversible, which makes repetitive treatment relatively safe. Several studies have shown encouraging clinical results of palliative therapy using bone seeking radiopharmaceuticals, with an overall reported pain response rate in the order of +/- 70-80% of patients. This systemic form of radionuclide therapy is simple to administer and complements other treatment options. It has been associated with marked pain reduction, improved mobility in many patients, reduced dependence on analgesics, and improved performance status and quality of life. Additionally, new therapeutic strategies hold the promise of enhancement of the palliative and anticancer effects of this form of therapy.
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PMID:Bone seeking radiopharmaceuticals for palliation of pain in cancer patients with osseous metastases. 1763 Sep 15

Background. The aim of this study was to evaluate the effectivness of connected therapy using strontium 89 or Sm153 (osteoblastic component) and bisphosphonate therapy (osteolytic component) in the group of breast cancer patients with multiple osteoblastic-osteolytic (mixt) bone metastases. <br /> Material and methods. The study included 16 patients with breast cancer and multiple bone painful metastases detected by scintigraphy and by radiogram or CT or MRI (the type of metastases). Each patient received a standard dose of strontium 89 (Metastron) or samarium 153 (Quadramet) combined with intravenous infusion of pamidronate (Aredia) or zoledronate (Zometa). The bisphosphonate therapy was repeated every month. For assessment of therapy effectivness; pain relief (VAS scale), a reduction in analgesic requirements and motor activity (ECOG and Karnofsky scale) were evaluated. The group of 10 patients treated with bisphosphonate only in the same time was observed. <br /> Results. We conclude that connected palliative therapy using strontium 89 and bisphosphonates is effective (66-75% "good" and "moderate" response rate) and safe for bone pain palliation in patients with multiple osteoblastic-osteolytic bone metastases from breast cancer. We have observed that the analgesic requirments decreased to 30% of dose on average. The motor activity of the points evaluated according to ECOG scale increased from 3 to 2 and from 50 to 60 to Karnofsky scale. <br /> Conclusions. The results of treatment in the group with radioisotope and bisphosphonate were better than in the group treated with bisphosphonates or radioisotope only.
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PMID:Preliminary results of combined application of radioisotopes and biphosphonates in the management of pain associated with osteoblastic-osteolytic bone metastases of breast cancer. 1803 12

Background. The aim of this study was to evaluate the effectivness of strontium 89 (Metastron) therapy in the group of prostate cancer patients with multiple bone metastases. <br /> Material and methods. The study included 70 patients (aged 53-84) with prostate cancer and multiple bone painful metastases detected by scintigraphy and by radiogram character of metastases (osteoblastic - 55 patients, osteolytic-osteoblastic - 15 patients). Before strontium 89 therapy 34 out 70 patients have been performed local irradiation to the back bone as prevention of spinal cord compression. For assessment of therapy effectivness; pain relief (VAS scale), a reduction in analgesic requirements and motor activity (ECOG and Karnofsky scale) were evaluated. <br /> Results. We conclude that palliative therapy using strontium 89 is effective (88% "good" and "moderate" response rate) and safe for bone pain palliation in patients with multiple prostate cancer bone metastases; it also improves the quality of life. We have observed that the analgesic requirments decreased to 50% of dose on average. The motor activity of the points evaluated according to ECOG scale and Karnofsky scale was much better (p < 0,05).
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PMID:The effectivness of strontium 89 in palliative therapy of painful prostate cancer bone metastases. 1803 33

Background. Bone metastases are observed in 30-70% of patients with cancer. Pain is most frequent symptom that requires regular control and treatment. Systemic palliative radionuclide therapy using beta-emitters is alternative method for analgetic drugs and external beam radiotherapy. The aim of the study was to establish efficacy and risk of side effects of radionuclide treatment in patients with painful osseous metastases. <br /> Material and methods. Sr-89 therapy was performed in 33 patients 13 women and 13 men aged 42 to 79 years (mean 61) with cancer and bone metastases confirmed in MDP-Tc99m whole body scan. Prostate cancer was primary tumour in 18 patients, breast cancer in 12, urinary bladder cancer in 2 and renal cancer in 1 patient. <br /> After intravenous administration of 150 MBq of strontium-89 chloride patients were observed during <br /> 3 months and more. Changes in blood counts, intensity of pain, drugs intake, life activity and duration of pain relief was evaluated from 0 to 3 points. Overall Response Index was very good if total points amounted 10-12, good - 7-9, satisfying - 4-6, poor - 2-3 and no response 0-1 points. Myelosuppression was evaluated according to Common Toxicity Criteria by WHO. <br /> Results. Very good response in 6 patients (18%), good in 15 (46%), satisfying in 6 (18%), poor in 2 (6%) and no response in 4 (12%) patients. Transient haemotoxicity post Sr-89 therapy was observed in 16 patients (48%), in 11 patients it was grade I CTC, in 1 grade II CTC, in 3 grade 3 CTC and in one man grade IV which required treatment. Duration of life after therapy was between 21 to 138 weeks (mean 58 weeks). Therapy was repeated in 16 (48%) patients after more than 3 months. Third dose was injected in 2 patients (6%). <br /> Conclusions. Palliative strontium-89 treatment of painful osseous metastases is effective therapy with very mild haemotoxicity.
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PMID:Strontium-89 in palliative treatement of painfull bone metastases. 1803 34

The objective of the present work is to apply the plasma clearance parameters to strontium, previously determined in our laboratory, to improve the biokinetic and dosimetric models of strontium-90 ((90)Sr) used in radiological protection; and also to apply this data for the estimation of the radiation doses from strontium-89 ((89)Sr) after administration to patients for the treatment of the painful bone metastases. Plasma clearance and urinary excretion of stable strontium tracers of strontium-84 ((84)Sr) and strontium-86 ((86)Sr) were measured in GSF-National Research Center for Environment and Health (GSF) in 13 healthy German adult subjects after intravenous injection and oral administration. The biological half-life of strontium in plasma was evaluated from 49 plasma concentration data sets following intravenous injections. This value was used to determine the transfer rates from plasma to other organs and tissues. At the same time, the long-term retention of strontium in soft tissue and whole body was constrained to be consistent with measured values available. A physiological urinary path was integrated into the biokinetic model of strontium. Parameters were estimated using our own measured urinary excretion values. Retention and excretion of strontium were modeled using compartmental transfer rates published by the International Commission on Radiological Protection (ICRP), the SENES Oak Ridge Inc. (SENES), and the Urals Research Center for Radiation Medicine (TBM). The results were compared with values calculated by applying our GSF parameters (GSF). For the dose estimation of (89)Sr, a bone metastases model (GSF-M) was developed by adding a compartment, representing the metastases, into the strontium biokinetic model. The related parameters were evaluated based on measured data available in the literature. A set of biokinetic parameters was optimized to represent not only the early plasma kinetics of strontium but also the long-term retention measured in soft tissue and whole body. The ingestion dose coefficients of (90)Sr were computed and compared with different biokinetic model parameters. The ingestion dose coefficients were calculated as 2.8 x 10(-8), 2.1 x 10(-8), 2.5 x 10(-8) and 3.8 x 10(-8) Sv Bq(-1) for ICRP, SENES, TBM and GSF model parameters, respectively. Moreover, organ absorbed dose for the radiopharmaceutical of (89)Sr in bone metastases therapy was estimated based on the GSF and ICRP biokinetic model parameters. The effective doses were 3.3, 1.8 and 1.2 mSv MBq(-1) by GSF, GSF-M, and ICRP Publication 67 model parameters, respectively, compared to the value of 3.1 mSv MBq(-1) reported by ICRP Publication 80. The absorbed doses of red bone marrow and bone surface, 17 and 21 mGy MBq(-1) calculated by GSF parameters, and 7.1 and 8.8 mGy MBq(-1) by GSF-M parameters, are comparable to the clinical results of 3-19 mGy MBq(-1) for bone marrow and 16 mGy MBq(-1) for bone surface. Based on the GSF-M model, the absorbed dose of (89)Sr to metastases was estimated to be 434 mGy MBq(-1). The strontium clearance half-life of 0.25 h from the plasma obtained in the present study is obviously faster than the value of 1.1 h recommended by ICRP. There are no significant changes for ingestion dose coefficients of (90)Sr using different model parameters. A model including the metastases was particularly developed for dose estimation of (89)Sr treatment for the pain of bone metastases.
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PMID:Influence of human biokinetics of strontium on internal ingestion dose of 90Sr and absorbed dose of 89Sr to organs and metastases. 1820 50

Prostate cancer metastasis is a unique disease. The propensity of prostate cancer to metastasize to bone and the prognostic significance of bone metastasis suggest that effective treatment of bone metastasis may provide clinical benefits. Both osteoblasts and osteoclasts have been shown to play a central role in the interactions between the metastatic prostate cancer cells and bone. Although most prostate cancer bone metastasis is osteoblastic, it remains unclear which cell type is initially involved in the process. Other components in the bone, such as the endothelium and stroma, may also play important roles in this process. The osteoblastic feature of prostate cancer bone metastasis has led to therapies focused on targeting osteoblast activity. Clinical trials targeting osteoblasts use radiopharmaceuticals (strontium-89 and samarium-153), the endothelin A receptor inhibitor atrasentan, or the vitamin D analog calcitriol. Agents that target osteoclasts include bisphosphonates; those that target endothelial cells include thalidomide and bevacizumab. Although these clinical trials for bone metastasis may provide effective treatments, novel concepts of how prostate cancer cells selectively metastasize to bone may advance our understanding and provide improved treatments for this difficult clinical problem. We propose a refined "seed" and "soil" view of metastasis. We speculate that in prostate cancer bone metastasis, the seed may comprise the so-called cancer stem cells, whereas the soil may comprise an onco-niche, ie, a unique microenvironment, that facilitate the growth and survival of cancer stem cells. If so, targeting cancer stem cells or the onco-niche may offer another way to improve treatment of prostate cancer bone metastasis.
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PMID:Current trials using bone-targeting agents in prostate cancer. 1830 81


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