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)

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

We report the PET-CT appearance of Zoledronate-related osteonecrosis of the mandible in a 54-year-old woman with right breast cancer with osseous and pulmonary metastases. Her treatment included surgery, chemotherapy and Zoledronate, and external beam radiation treatment. During the course of treatment, the patient developed osteonecrosis of the jaw secondary to Zoledronate, which was biopsy-proven, for which Zoledronate was discontinued shortly after. Hybrid PET-CT was performed approximately 1 year after the discontinuation of Zoledronate. PET-CT images demonstrated diffuse, intense hypermetabolism in the mandible, consistent with documented osteonecrosis.
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PMID:Zoledronate-related osteonecrosis of the mandible. 1809 68

Many solid tumors metastasize to bone, leading to debilitating skeletal complications such as intractable bone pain and pathologic fractures. Patients who experience a skeletal-related event (SRE) are at higher risk for subsequent events. After an SRE such as a pathologic fracture, spinal cord compression, or the requirement for orthopedic surgery or palliative radiation therapy, a patient's quality of life and functional independence could decline substantially. Prevention or delay of skeletal complications provides clinical benefit to patients with bone metastases secondary to solid tumors. Treatment for the prevention of the first SRE might substantially improve patients' quality of life, functional independence, and pain throughout the course of their disease. Bisphosphonates have shown a palliative benefit in this setting. In particular, zoledronic acid is the only bisphosphonate that has provided benefits for patients with bone metastases secondary to a broad range of solid tumors. Among patients with metastatic breast or prostate cancer, zoledronic acid has demonstrated significant reductions in pain and skeletal morbidity compared with placebo. Zoledronic acid has also shown significant reductions in skeletal morbidity in patients with lung cancer or other solid tumors compared with placebo. Pamidronate, oral clodronate, and ibandronate compared with placebo have each shown significant benefits in reductions of pain and skeletal complications for patients with metastatic breast cancer. Further improvements in the management of skeletal health in patients with malignant bone disease could be achieved through ongoing bisphosphonate investigations to optimize dose, timing, and duration of treatment.
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PMID:Treatment of bone metastases and bone pain with bisphosphonates. 1863 73

Bone metastases are common in patients with advanced-stage cancer; they can lead to skeletal complications (ie, pathologic fractures, spinal cord compression, tumor-induced hypercalcemia, and severe bone pain) that often require orthopedic surgery or palliative radiation therapy and negatively affect quality of life. The primary role of bisphosphonates for the management of bone metastases in patients with advanced-stage cancer is the prevention of these painful skeletal complications. In placebo-controlled trials, a number of bisphosphonates, including oral clodronate, oral and intravenous (I.V.) ibandronate, I.V. pamidronate, and I.V. zoledronic acid, have been shown to significantly reduce skeletal complications in patients with bone metastases from breast cancer. Furthermore, zoledronic acid provided benefit compared with pamidronate in patients with bone metastases from breast cancer in a large, comparative trial. Zoledronic acid also provided long-term benefits in randomized placebo-controlled trials in patients with bone metastases from prostate cancer, lung cancer, and other solid tumors, whereas other bisphosphonates that have been investigated have failed to demonstrate objective long-term benefits in placebo-controlled trials. In addition, although systemic analgesics and radiation therapy are primary treatments for the management of bone pain, bisphosphonates can also play an important secondary role in reducing bone pain associated with skeletal metastases. Notably, several economic analyses of bisphosphonate therapy have demonstrated that these agents are cost-effective by reducing health-care costs associated with skeletal complications and providing clinically significant quality of life benefits to patients with malignant bone disease.
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PMID:Role of bisphosphonates for the management of skeletal complications and bone pain from skeletal metastases. 1863 88

Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the efficacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE), osteoporotic complications, and palliation of bone pain, among others. Zoledronic acid is the only bisphosphonate effective in decreasing SREs associated with bone metastases from advanced renal cell carcinoma and prostate cancer. Regarding prostate cancer, zoledronic acid effectively prevents both bone loss in patients with locally advanced disease receiving androgen deprivation therapy and SREs in men with hormone-refractory or hormone-sensitive metastatic disease. Zoledronic acid has an acceptable safety profile and tolerability, and has been effective at significantly decreasing the incidence, delaying the onset, and reducing the overall risk of experiencing an SRE compared to placebo. It is the only bisphosphonate currently approved for the prevention and treatment of skeletal complications in patients with bone metastases due to all solid tumors.
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PMID:Zoledronic acid in the management of metastatic bone disease. 1872 15

Bisphosphonates (BPs), as inhibitors of osteoclasts, are widely used in the management of metastatic bone disease and in the prevention of osteomalacia and osteoporosis. Recent cases of bone necrosis of the jaws have been associated with the use of bisphosphonate therapy. A case is presented of a patient with osteonecrosis of the maxilla with a history of long-term bisphosphonate therapy for metastatic breast cancer. The authors treated the patient and suggest appropriate patient management guidelines with reference to current knowledge. Although a definitive treatment for bisphosphonate-associated osteonecrosis has not yet been established, clinicians must be aware of the pharmacologic properties of several bisphosphonates currently available and their indications, susceptible risk factors in the development of osteonecrosis of the jaws, the clinical signs and symptoms, and recommendations for patient management, including prevention and early recognition. BPs, potent inhibitors of osteoclast-mediated bone resorption, were first introduced more than 20 years ago. Since then, they have been used widely in the management of bone diseases, including hypercalcemia related to malignancy, myeloma-related bone disease, Paget's disease and osteoporosis. They have also been shown to inhibit tumor cell proliferation and inhibit angiogenesis. These additional features have made BPs useful in the treatment of metastatic disease, including breast and prostate cancer, resulting in a rise in the medical use of these drugs. However, recent reports suggest that BPs, particularly the nitrogen-containing BPs pamidronate (Aredia) and zoledronic acid (Zometa), both manufactured by Novartis of East Hanover, NJ, are capable of causing bisphosphonate-associated osteonecrosis of the jaw (BON). With 2.5 million patients treated with pamidronate and/or zoledronate worldwide, BON occurs in about one per 10,000 treated patients (Novartis, unpublished data, 2004). Currently, the total number of reported cases associated with alendronate (Fosamax, Merck and Co. Inc., White-house Station, NJ) the most commonly prescribed oral bisphosphonate, is approximately 170 worldwide (C. Arsver, oral communication, March 2006). This corresponds to a spontaneous BON incidence of approximately 0.7 cases per 100,000-years exposure. However, there is insufficient data to determine why the osteonecrosis reported seems to particularly affect the jaw, with a slightly higher rate in the mandible than the maxilla. This report concerns the management of a patient with BON. Information provided includes: the pharmacologic properties of the several bisphosphonates currently available; the pathobiological mechanism; the clinical presentation of the oral lesions; and recommendations for the oral management of patients who have received BP therapy, with consideration of a preventative approach based on current knowledge.
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PMID:Bisphosphonate-associated osteonecrosis: a clinician's reference to patient management. 1876 52

We report a case of regression of pulmonary and bony metastases in a patient with malignant melanoma following palliative treatment with systemic zoledronate and localised radiotherapy to the bone. Zoledronate is a potent new bisphosphonate used for the treatment of metabolic bone diseases including bone metastases due to its inhibitory effect on osteoclasts. In the context of metastatic cancer zoledronate is routinely used to improve bone pain and reduce the frequency of skeletal events. There is also an increasing body of evidence suggesting that bisphosphonates exhibit anti-tumour properties. Bisphosphonates are able to activate Vgamma9Vdelta2 gamma-delta T cells which can be key players in the immune defence against malignant cells. Furthermore bisphosphonates have direct anti-proliferative, anti-metastatic and pro-apoptotic effects on tumour cells. These actions, together with their low side effect profile, may prove to be useful therapeutic tools in the treatment of cancer even in the absence of bone metastases. On the basis of this case report we here review the current literature on present preclinical and clinical studies using bisphosphonates for the treatment of cancer.
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PMID:Regression of melanoma metastases following treatment with the n-bisphosphonate zoledronate and localised radiotherapy. 1925 Aug 73

Bisphosphonates are widely used as therapeutic agents in bone disorders including cancer metastasis due to their osteoclast inhibitory effect. Recent data shows that bisphosphonates may also induce bone-building by stimulating osteoblast activity. Clinical observations, however, have revealed that bisphosphonates may cause necrosis in the oral cavity which questions their usefulness in bone regeneration during the consolidation of inorganic implants. Here we report the investigation of bone neogenesis following chronic amine bisphosphonate (Zometa) treatment in a novel experimental model, using the rat tail vertebra as a support. This method involves (1) implantation of titan screw into the tail vertebrae, (2) systemic bisphosphonate treatment and (3) quantitative biophysical measurements which mirrors consolidation of implant, i.e. strength of fixation and changes in newly formed bone architecture using micro Computer Tomograph (micro-CT). The degree of fixation of titan implants (osseointegration) increased by 36% on the effect of Zometa and the structure of newly formed bone became robust. The mass of new bone increased 3.1-fold at 6 weeks of regeneration, as compared to controls. Thus, Zometa, a potent aminobisphosphonate used in therapy of cancer metastases, osteoporosis and bone marrow transplantation, significantly increased bone neogenesis and enforced osseointegration of titan implants as measured quantitatively in the rat tail vertebra. Our data support the usefulness of aminobisphosphonates in the rehabilitation of bone loss as well as in improvement osseointegration of implants. We emphasise that this novel method may open up new possibilities for screening the effects of local and systemic treatments.
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PMID:Aminobisphosphonate stimulates bone regeneration and enforces consolidation of titanium implant into a new rat caudal vertebrae model. 1926 22

Abstract Bone-seeking radiopharmaceuticals and bisphosphonates may be indicated in patients with cancer with painful osseous metastases to palliate pain symptoms or to prevent skeletal-related events. Both pharmaceuticals may have an additive or even synergistic palliative effect. The combined use of bone-seeking radiopharmaceuticals and bisphosphonates is, however, controversial because of assumed competition between both phosphonate-compounds at the bone level. We report a case of hormone-refractory prostate cancer (HRPC) with multiple painful osseous metastases. The patient was treated with samarium-153-ethylenediaminetetramethylphosphonic acid ((153)Sm-EDTMP; Quadramet, CIS bio International, Saclay, France) in combination with zoledronic acid (Zometa, Novartis, Stein, Switzerland). He was treated for 6 months with 4 weekly intervals of zoledronic acid in combination with 3 monthly intervals of (153)Sm-EDTMP. No negative interaction was found, toxicity was low, and efficacy high. He experienced a total relief of pain, a significant decrease of prostate-specific antigen (PSA) and, surprisingly, a significant decrease of tumor burden.
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PMID:Treatment of painful bone metastases in hormone-refractory prostate cancer with zoledronic acid and samarium-153-ethylenediaminetetramethylphosphonic acid combined. 1959 54

The anti-estrogen treatment for hormone-sensitive breast cancer and the androgen deprivation therapy for prostate cancer can lead to the development of osteoporosis and bone fractures. Metastases associated with prostate and breast cancer can also occur in bone. Bisphosphonates are used in these types of bone dysfunction. Zoledronic acid is the most potent bisphosphonate. In osteoporosis, zoledronic acid inhibits bone reabsorption and increases bone mineral density for at least a year after intravenous administration. The efficacy and safety of zoledronic acid in osteoporosis secondary to hormone-sensitive cancers (prostate and breast), and in the bone metastases associated with these cancers are reviewed.
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PMID:Clinical efficacy and safety of zoledronic acid in prostate and breast cancer. 1976 24


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