Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone is a preferred site of metastasis for many solid tumors, and the complications associated with bone metastases can result in significant skeletal morbidity including severe bone pain, pathologic fracture, spinal cord compression, and hypercalcemia of malignancy (HCM). Bisphosphonates are the current standard of care for preventing skeletal complications associated with bone metastases. Clinical trials investigating the benefit of bisphosphonate therapy have used a composite end point defined as a skeletal-related event (SRE) or bone event, which typically includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and HCM. Bisphosphonates have been shown to significantly reduce the incidence of these events in patients with bone metastases. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ), pamidronate (Aredia; Novartis Pharmaceuticals Corp.), clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ), and ibandronate (Bondronat; Hoffmann-La Roche Inc.; Nutley, NJ) all have demonstrated efficacy superior to that of placebo in patients with breast cancer. Zoledronic acid is the only bisphosphonate that has been compared directly with pamidronate, and it was shown by multiple event analysis to be significantly more effective at reducing the risk of an SRE. In patients with prostate cancer, clodronate, etidronate (Didronel; Procter and Gamble Pharmaceuticals, Inc.; Cincinnati, OH), and pamidronate have demonstrated transient palliation of bone pain. However, zoledronic acid is the only bisphosphonate to demonstrate both significant and sustained pain reduction and a significantly lower incidence and longer time to onset of SREs compared with placebo. Zoledronic acid is also the only bisphosphonate to demonstrate efficacy in patients with bone metastases from a variety of other solid tumors, including lung cancer and renal cell carcinoma. In conclusion, bisphosphonates effectively reduce skeletal complications in patients with bone metastases from breast cancer, and zoledronic acid has demonstrated the broadest clinical activity in patients with a wide variety of tumor types.
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PMID:Bisphosphonates: clinical experience. 1545 26

Men with advanced prostate cancer are at high risk for developing bone metastases, which result in clinically significant skeletal morbidity. Treatments that prevent skeletal complications in these patients could considerably improve their quality of life. Therefore, this paper reviews the role of bisphosphonates in the treatment of hormone-refractory prostate cancer (HRPC). Published studies were identified through MEDLINE searches, review of bibliographies of relevant articles, and review of abstracts from scientific meetings. Metastatic bone disease in men with HRPC results in skeletal complications such as pathologic fractures, spinal cord compression, and debilitating bone pain. First- and second-generation bisphosphonates, clodronate and pamidronate, had transient palliative effects that were not durable and did not prevent skeletal events in these patients. A small open-label study of ibandronate demonstrated significant reductions in pain, but these results have not been confirmed in a larger, randomized, controlled trial. To date, zoledronic acid is the only bisphosphonate that has demonstrated a statistically significant reduction in skeletal morbidity in this patient population. In a large, multicenter, randomized, placebo-controlled trial, treatment of men with HRPC and bone metastases with zoledronic acid significantly reduced skeletal-related events and provided a durable reduction of bone pain over 24 months compared with placebo. Zoledronic acid is the only bisphosphonate that has demonstrated efficacy for preventing skeletal complications in patients with HRPC and bone metastases. Therefore, initiation of zoledronic acid therapy should be considered to prevent skeletal morbidity and improve the quality of life of these patients.
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PMID:The role of bisphosphonates in hormone-refractory prostate cancer. 1566 71

Patients with bone metastases from breast cancer often experience substantial skeletal complications -- including debilitating bone pain -- which negatively affect quality of life. Zoledronic acid (4 mg) has been demonstrated to reduce significantly the risk of skeletal complications in these patients and is administered via a short, 15-min infusion every 3 weeks, allowing the possibility for home administration. This study compared the efficacy and safety of zoledronic acid administered in the community setting vs the hospital setting in breast cancer patients with > or =1 bone metastasis receiving hormonal therapy. After a lead-in phase of three infusions of 4 mg zoledronic acid in the hospital setting, 101 patients were randomized to receive three open-label infusions in the community or hospital setting, followed by three infusions in the opposite venue (a total of nine infusions). The Brief Pain Inventory (BPI) and the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) were used to assess potential benefits of zoledronic acid therapy. At study end, analysis of the BPI showed significant reductions in worst pain (P=0.008) and average pain in the last 7 days (P=0.039), and interference with general activity (P=0.012). In each case, there were significantly greater improvements in pain scores after treatment in the community setting compared with the hospital crossover setting for worst pain (P=0.021), average pain (P=0.003), and interference with general activity (P=0.001). Overall global health status showed a significant median improvement of 8.3% (P=0.013) at study end. Physical, emotional, and social functioning also showed significant overall improvement (P=0.013, 0.005, and 0.043, respectively). Furthermore, physical, role, and social functioning showed significantly greater improvements after treatment in the community setting compared with the hospital crossover setting (P=0.018, 0.001, and 0.026, respectively). There was no difference between hospital and community administration in renal or other toxicity, with zoledronic acid being well tolerated in both treatment settings. These data confirm the safety and quality-of-life benefits of zoledronic acid in breast cancer patients with bone metastases, particularly when administered in the community setting.
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PMID:Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration. 1587 Jul 21

Bisphosphonates have an antiosteolytic effect by the inhibition of osteoclastic action. Although the exact mode of action is not completely understood, major progress on both the cellular and molecular levels has been made in recent years. Bisphosphonates alleviate pain and reduce complications, such as pathologic fractures, or hypercalcemia. Dental and periodontal research has shown great interest in clinical applications of bisphosphonates' antiosteolytic and antiosteoclastic traits, since they can be applied to counteract bone loss in chronic periodontitis. Investigations have associated avascular necrosis events in the jawbones with bisphosphonate therapy. Maxillary and mandibular osteonecrotic foci accompanied by pain, inconvenience and purulent exudates were incidentally found in patients who were taking pamidronate (Aredia), zolendronate (Zometa) and even alendronate (Fosalan). Our institutional database search over the past year yielded ten patients who were admitted to the Oral and Maxillofacial Surgery Unit at the Tel Aviv Sourasky Medical Center, due to an osteonecrotic bone lesion coupled with a prior history of bisphosphonate therapy. All these patients also had a recent dental extraction. They were all treated according to the osteomyelitis protocol, and their response to therapy varied from several weeks to many months, with some cases requiring repeat surgical intervention (curettage or sequestrectomy). This article strives to alert on the possible linkage between drug therapy using bisphosphonates and the serious event of avascular jawbone necrosis. The important role of the oral surgeon in following up on this group of patients should not be underestimated.
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PMID:[Avascular necrosis of the jaw bone after bisphosphonate therapy]. 1614 48

Bone metastases are a major cause of cancer morbidity. Bone metastases are associated with pain, fractures, spinal cord compression, ineffective haematopoiesis, and hypocalcaemia of malignancy. The goals of treatment for bone metastases are to prevent disease-related skeletal complications, palliate pain, and maintain quality of life. Bisphosphonates are a standard part of supportive care for patients with bone metastases. Zoledronic acid, a nitrogen containing third generation bisphosphonate, is the most active and is the most thoroughly investigated bisphosphonate for metastatic bone disease. The efficacy and safety of zoledronic acid has been established in three pivotal prospective, randomized controlled trials involving more than 3000 subjects. The evidence is reviewed here with a focus on clinical relevance. Across a broad array of tumour types, zoledronic acid (4 mg intravenously over 15 min every 3-4 weeks) decreased the frequency of skeletal-related events, delayed the time to a first skeletal-related event, and reduced pain. Zoledronic acid is more effective than pamidronate in breast cancer and the only bisphosphonate proven effective for metastatic prostate cancer, lung cancer, renal cell carcinoma and other solid tumours.
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PMID:Zoledronic acid to prevent skeletal complications in cancer: corroborating the evidence. 1622 55

Bone metastases are a major cause of morbidity for men with prostate cancer. Complications of bone metastases include pain, fractures, and spinal cord compression. Although they appear osteoblastic by radiographic imaging, most bone metastases are characterized by excess osteoclast number and activity. In addition, pathologic osteoclast activation is associated with increased risk of skeletal complications. Zoledronic acid, a potent inhibitor of osteoclast activity, differentiation, and survival, decreases the risk of skeletal complications in men with androgen-independent prostate cancer and bone metastases. Other bisphosphonates, including pamidronate and clodronate, seem to be ineffective in this setting. The reduction in risk of skeletal complications with zoledronic acid must be weighed against potential adverse effects. Additional studies are needed to determine the optimal timing, schedule, and duration of treatment in men with bone metastases as well as the potential role of bisphosphonates in other settings including the prevention of bone metastases.
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PMID:Bisphosphonates for treatment and prevention of bone metastases. 1627 76

Zoledronic acid is a bisphosphonate that is effective in the treatment of complications of metastatic bone disease. We have carried out a perspective study on 24 consecutive patients with prostate cancer metastatic to bone to verify the effect of zoledronic acid on analgesic response and a possible relationship with the levels of bone metabolism biomarkers. Eligibility for this study required prostate cancer patients with metastatic bone disease and pain not controlled by analgesics. Patients were excluded from the study if they were receiving cytotoxic chemotherapy or radiation therapy within three months. Eighteen patients (75%) were considered responder to acid zoledronic, only 6 patients did not respond. Before starting treatment (T0) mean Visual Analogue Scale was 7.8 (SE +/- 0.29), after 1 month therapy (T1) was 3.6 (SE +/- 0.3) and after three months (T2) was 3.1 (SE +/- 0.4) with a significant difference between T0 and T1 (p<0.0005) and between T0 and T2 (p<0.0005). Visual Analogue Scale improvement was positively correlated with decrease of C-telopeptide and bone phosphatase alkaline (p<0.05) serum levels.
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PMID:The use of zoledronic acid in patients with bone metastases from prostate carcinoma: effect on analgesic response and bone metabolism biomarkers. 1632 46

Paget's disease is a relatively common high-turnover metabolic bone disease that can serve as a model for osteoporosis and other metabolic bone diseases in investigation of therapeutic strategies to normalize bone turnover. Aims of treatment include rapid normalization of bone formation and resorption to prevent loss of mechanical integrity. Treatment will also reduce pain, while long-term maintenance of normal turnover may prevent long-term complications. Newer bisphosphonates have high antiresorptive potency and increased retention in bone, permitting a strategy of intermittent intravenous (IV) administration in achieving and maintaining normal bone turnover. In pivotal zoledronic acid Paget's disease trials, patients received a single 15-min IV infusion of zoledronic acid 5 mg (ZOL 5 mg) or risedronate 30 mg/day orally for 2 months. Treatment with ZOL 5 mg was associated with significant improvement in serum alkaline phosphatase, normalization in both the short and long term, and significant prolongation of biochemical therapeutic response in long-term follow-up. No changes in serum creatinine levels were observed with either treatment, and no clinically significant renal abnormalities were reported. Intermittent IV administration of potent bisphosphonates constitutes an intriguing strategy for treatment of Paget's disease and other metabolic bone diseases.
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PMID:Pharmacological therapy of Paget's and other metabolic bone diseases. 1640 63

Current therapies have extended the survival of patients with prostate cancer. However, these patients often develop skeletal morbidity from disease- and treatment-related effects that undermine skeletal integrity throughout the course of the disease. Low bone mineral density (BMD) is prevalent in patients with early-stage prostate cancer, and androgen-deprivation therapy by either pharmaceutical agent (including hormonal) or surgical castration causes significant decreases in BMD. Fractures can result in a loss of independence and have been associated with shorter survival in patients with prostate cancer. Zoledronic acid is the only bisphosphonate that has demonstrated objective and long-term benefits in reducing skeletal morbidity in patients with bone metastases due to prostate cancer, and it has produced long-term reductions in pain levels compared with placebo in this setting. Therefore, bisphosphonates, particularly zoledronic acid, may provide important benefits for preserving bone health during the course of prostate cancer progression.
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PMID:The role of bisphosphonates in the management of prostate cancer. 1661 87

For a long time, hormone-refractory prostate cancer was regarded as a chemoresistant tumor. The introduction of taxanes has prompted a change in this opinion. For the first time treatment with 75 mg/m(2) docetaxel every 3 weeks has evidenced a survival benefit in a phase III trial (median survival of 18.9 months versus 16.5 months with mitoxantrone). Further advantages were improved pain reduction and quality of life. Neutropenia was foremost among the side effects. Docetaxel is currently the standard treatment for hormone-refractory prostate cancer. The morbidity of metastatic hormone-refractory prostate cancer is influenced by bone metastases. Pain is a prominent feature. Skeletal complications are frequent. Therapy with 4 mg zoledronic acid reduced skeletal complications significantly in comparison to placebo. The most pronounced effect is the reduction of pathological fractures. Side effects include flu-like symptoms, muscle pain, and edemas. Zoledronic acid also belongs to the standard treatment of hormone-refractory prostate cancer with bone metastases.
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PMID:[Therapeutic options for hormone-refractory prostate cancer]. 1671 Jun 77


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