Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Physical exercise is becoming an accepted part of therapy for many patients with cancer. Exercise may alleviate patients' fatigue and improve physical performance and psychological outlook. Much of the research is limited to women with breast cancer and excludes patients with bone metastases. This article reports on the authors' work in facilitating exercise adherence for patients with multiple myeloma (MM) and bone lesions while they were enrolled in a feasibility/pilot exercise study as they were receiving treatment for their disease in an outpatient treatment program. The exercise program for these patients receiving high-dose chemotherapy and stem cell transplantation consisted of aerobic and strength-building components. The program was home based, and patients performed exercises without direct supervision. On average, the patients completed the six-month exercise prescription 75% of the time. Overall trends showed that all 14 patients in the exercise group improved in several areas of testing, and the test results of all 10 patients in the usual-care group declined. Flexibility and simplicity are essential when designing exercise programs for patients, and encouragement and support also are needed to help patients adhere to prescribed exercise.
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PMID:Facilitating exercise adherence for patients with multiple myeloma. 1460 49

Painful and life-threatening skeletal complications are common in patients with advanced cancer metastatic to bone. Patients with breast cancer and multiple myeloma who survive for 2 or more years after developing bone metastases/lesions are at chronic risk for skeletal complications. Patients with prostate cancer and other solid tumors are also at high risk for skeletal complications, and, until recently, no effective treatment had been identified. Zoledronic acid, a new-generation bisphosphonate, was recently shown to be safe and effective as treatment for the prevention of skeletal complications in three randomized, phase III trials involving more than 3000 patients with multiple myeloma, breast, prostate, and lung cancers, and other solid tumors. Zoledronic acid (4 mg) was at least as effective as pamidronate (90 mg) in preventing skeletal complications in the overall study population of patients with breast cancer and multiple myeloma and was superior to pamidronate in the subset of over 1000 patients with breast cancer. In patients with solid tumors, including prostate cancer and lung cancer, zoledronic acid significantly reduced the incidence and delayed the onset of skeletal complications compared with placebo. Zoledronic acid is the first bisphosphonate with broad clinical utility and may become the preferred bisphosphonate for the treatment of bone metastases in patients with advanced cancers.
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PMID:Zoledronic acid for the treatment of bone metastases in patients with breast cancer and other solid tumors. 1461 36

Many advanced cancers, particularly breast cancer and prostate cancer, metastasize to the bone, resulting in painful lesions and skeletal complications. Intravenous bisphosphonate therapy is an important component of palliative care for patients with bone metastases, and pamidronate has been the standard of care for patients with breast cancer and multiple myeloma since 1996. However, zoledronic acid is the first bisphosphonate shown to significantly reduce skeletal morbidity in patients with a wide range of primary tumor types. Zoledronic acid has demonstrated efficacy in the management of hypercalcemia and metastatic bone disease. In phase III studies involving more than 3000 patients with multiple myeloma, breast cancer, prostate cancer, lung cancer, and other cancers, 4 mg zoledronic acid demonstrated consistent efficacy across a range of clinical end-points, and was safe and well tolerated when infused over 15 min. Based on these studies, zoledronic acid appears to be active in patients with bone metastases irrespective of tumor type, and should be considered as the standard of care for the treatment of bone metastases.
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PMID:Proven efficacy of zoledronic acid in the treatment of bone metastases in patients with breast cancer and other malignancies. 1465 40

Patients with metastatic cancer and bone involvement are at chronic risk of skeletal complications, including bone pain, fractures, spinal cord compression and hypercalcaemia of malignancy. Therapies targeting the primary malignancy are often unable to prevent skeletal complications, which often require orthopaedic surgery, radiation therapy and analgesics. Intravenous bisphosphonates can reduce the risk of skeletal complications and the requirement for palliative radiation therapy. Since its broad regulatory approval, zoledronic acid (ZOMETA, Novartis Pharma AG/Novartis Pharmaceuticals Corporation) 4 mg by 15-minute intravenous infusion has become widely used to treat bone metastases from all solid tumours and is becoming the standard of care for advanced breast cancer and multiple myeloma. Additionally, cancer treatment-induced bone loss is an emerging problem in clinical oncology, and bisphosphonates -- particularly intravenous bisphosphonates -- may provide benefits even before bone lesions develop. Further investigations of bisphosphonates in these and other indications are ongoing.
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PMID:Bisphosphonate therapy in the oncology setting. 1466

The skeleton is the third most common site for cancer to spread to after the liver and lungs. Malignancies that can cause destruction of skeletal bones include multiple myeloma and metastatic disease of the breast, prostate, and lung. Bone metastases are problematic for patients with cancer because accelerated bone breakdown occurs with many associated complications. One or more of the following problems may occur: pain, hypercalcemia, pathologic fractures, myelosuppression, and spinal cord compression with subsequent progressive immobility. Quality of life is affected negatively, and associated feelings of fear, grief, anger, despair, anxiety, and depression can occur. Management of malignancies of the bone involves a multimodal approach. Therapies include analgesia, hormone therapy, chemotherapy, surgery, radiation therapy, and the use of bisphosphonates. Nurses can be instrumental in promoting positive outcomes for patients with bone metastases.
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PMID:Advances in the treatment of bone metastases. 1470 79

Pain from bone metastases limits mobility and may cause pathological fractures that can seriously impair the patient's quality of life. Conservative treatments such as orthopedic fixation, radiotherapy, and opioids sometimes fail to give satisfactory pain relief. Bisphosphonates have been reported to reduce the severity of pain from bone metastasis due to breast cancer, prostate cancer, and multiple myeloma. Recent clinical reports demonstrated the effectiveness of bisphosphonates in reducing pain from bone metastases in various malignancies. This study presents 3 cases of refractory pain from bone metastases due to thyroid, colorectal and hepatocellular carcinoma. Primary treatment included orthopedic fixation, radiotherapy, and/or parenteral opioids that failed to reduce bone pain. Bisphosphonate therapy was considered at the start of pain control treatment using opioids. All 3 cases showed gradual reduction in pain after i.v. pamidronate administration and allowed physicians to control further pain with opioids. In 1 case, the patient was successfully withdrawn from opioids. The role of bisphosphonates in painful bone metastases remains unclear. However, recent encouraging reports have indicated that bisphosphonate may become one of the adjuvant treatments available to control refractory bone pain from various malignancies.
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PMID:[Bisphosphonate as an adjuvant therapy for the pain of bone metastases, 3 cases]. 1499 67

Zoledronic acid (Zometa), a parenteral bisphosphonate, is an inhibitor of osteoclast-mediated bone resorption and is used in the management of patients with cancer. Zoledronic acid 4 mg is administered as an intravenous infusion over 15 minutes. In the treatment of bone metastases, zoledronic acid is the first and only bisphosphonate to demonstrate efficacy in patients with a broad range of tumour types and in multiple myeloma. In well-designed trials, a single 4 mg dose of zoledronic acid showed good efficacy in the treatment of patients with hypercalcaemia of malignancy. Zoledronic acid 4 mg was superior to pamidronic acid 90 mg, administered as a 2-hour infusion, as assessed by normalised serum calcium concentrations 10 days after administration. In conjunction with antineoplastic therapy, zoledronic acid was an effective long-term (up to 25 months) treatment for skeletal-related events in patients with bone metastases associated with multiple myeloma or solid tumours. In patients with bone metastases secondary to breast cancer or bone lesions from myeloma, zoledronic acid was at least as effective as pamidronic acid, based on assessments of skeletal-related events 25 months after the start of treatment. In addition, compared with pamidronic acid, the overall risk of developing skeletal complications, including hypercalcaemia of malignancy, was significantly reduced in recipients of zoledronic acid. Compared with pamidronic acid, zoledronic acid reduced the risk of patients with breast cancer developing a skeletal-related event by an additional 20%. Zoledronic acid was significantly more effective than placebo on most efficacy measures in patients with bone metastases secondary to other solid tumours (e.g. lung, prostate) and showed sustained efficacy for up to 15 months. Preliminary data indicate that its efficacy in these patients is sustained for up to 24 months. Estimates of the cost effectiveness of zoledronic acid in the treatment of prostate cancer were consistent with those of other bisphosphonates, and cost-effectiveness ratios were within limits considered acceptable economic value. Zoledronic acid was generally well tolerated, with a tolerability profile similar to that of pamidronic acid and placebo. As with other bisphosphonates, deterioration of renal function has occasionally been reported in patients receiving zoledronic acid and monitoring of serum creatinine is recommended during treatment. The efficacy of zoledronic acid is therefore well established in patients with hypercalcaemia of malignancy and, for up to 25 months, in the treatment of complications arising from metastatic bone disease in patients with multiple myeloma or solid tumours. The clinical profile of zoledronic acid compares favourably with that of pamidronic acid in patients with cancer and zoledronic acid has a more convenient administration schedule with the potential for better compliance. Thus, zoledronic acid is an effective bisphosphonate and is positioned to play an important role in the management of advanced cancer patients with bone metastases.
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PMID:Zoledronic acid: a review of its use in patients with advanced cancer. 1516 27

Bisphosphonate drugs are a group of pyrophosphate analogues which bind avidly to hydroxyapatite bone mineral surfaces and their major action is to inhibit osteoclast activity and thus bone resorption. In oncology, their role in metastatic bone disease is well established, but there is increasing interest in their potential role in preventing and treating cancer-induced bone loss and their possible anti-tumour effects. Metastatic bone disease is associated with a variety of skeletal complications, including pathologic fractures, bone pain, impaired mobility, spinal cord compression and hypercalcaemia. Intravenous bisphosphonates, particularly zoledronic acid, in conjunction with rehydration, are now established as the treatment of choice for hypercalcaemia. For treatment of bone pain, it has also been shown that bisphosphonates can be an effective supplementary approach to radiotherapy. In breast cancer and myeloma, bisphosphonates have now become part of standard therapy to treat and prevent skeletal-related events (SRE) and, until recently, treatment was largely with intravenous pamidronate or oral clodronate. However, large, randomised, multicentre trials using intravenous administration of the highly potent bisphosphonate zoledronic acid every 3-4 weeks have recently demonstrated a reduction of 20% in the risk of developing an SRE compared with pamidronate for patients with breast cancer. Moreover, these trials have demonstrated, for the first time, that a bisphosphonate significantly reduces the occurrence of skeletal events in hormone-refractory prostate cancer and in non-small cell lung cancer and a range of other solid tumours. Investigations into the potential of the relatively low potency bisphosphonate, clodronate, for the prevention of bone metastases in breast cancer have produced conflicting data. Further large, randomised studies with clodronate and zoledronic acid are planned and until the results are available it is not possible to identify a definite adjuvant role for bisphosphonates. Evidence is accumulating in vitro that bisphosphonates are also able to directly affect tumour cells, in addition to their effects on osteoclasts, with zoledronic acid being particularly potent. Over recent decades there has been a significant improvement in cure rates and survival times in certain cancers and the use of chemotherapy and hormone therapy has expanded greatly, leading to increasing numbers of long-term survivors who have received these treatments. Management of treatment-induced bone loss is therefore assuming a greater importance and bisphosphonates represent an attractive treatment option in such patients. Several placebo-controlled trials using oral clodronate, oral risedronate, intravenous pamidronate and intravenous zoledronic acid have all now demonstrated benefits in reducing the loss in bone mineral density.
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PMID:The role of bisphosphonates in breast and prostate cancers. 1516 99

Skeletal morbidity, including hypercalcemia of malignancy (HCM), places a severe burden on patients with advanced cancers. Bisphosphonates effectively correct HCM and reduce skeletal morbidity in patients with bone metastases. However, with the widespread use of bisphosphonates, the safety and convenience of therapy are emerging concerns. The delivery of effective doses of early bisphosphonates required a lengthy 24-hour i.v. infusion protocol because of renal tolerability issues. The introduction of more potent bisphosphonates with superior tolerability profiles has allowed therapy to be safely delivered via shorter i.v. infusions. Intravenous therapy with etidronate, clodronate, pamidronate, ibandronate, and zoledronic acid has been used to treat HCM and skeletal complications in cancer patients. Of these therapies, zoledronic acid (which can be safely administered via a 15-minute i.v. infusion) is the most convenient and effective and has demonstrated an excellent safety profile with long-term use. Zoledronic acid has also received the broadest regulatory approval of any bisphosphonate and can be used to treat HCM or bone lesions secondary to multiple myeloma and a wide variety of solid tumors, including breast, prostate, and lung cancers. In addition to the patient preference for shorter infusion times, the 15-minute i.v. infusion protocol of zoledronic acid can provide benefits for infusion centers by potentially increasing patient throughput.
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PMID:Safety and convenience of a 15-minute infusion of zoledronic acid. 1585 82

Bisphosphonates are endogenous pyrophosphate analogs in which a carbon atom replaces the central atom of oxygen. They are indicated in non-neoplastic diseases including osteoporosis, corticosteroid-induced bone loss, Paget disease, and in cancer-related diseases such as neoplastic hypercalcemia, multiple myeloma and bone metastases secondary to breast and prostate cancer. There is now extensive in vitro evidence suggesting a direct antitumor effect of bisphosphonates at different levels of action. Some new in vitro and in vivo studies support the cytostatic effects of bisphosphonates on tumor cells, and the effects on the regulation of cell growth, apoptosis, angiogenesis, cell adhesion, and invasion, with particular attention to biological properties. Well designed clinical trials are necessary to investigate whether the antitumor potential of bisphosphonates may be clinically relevant. On the basis of their effects on macrophages, we may divide bisphosphonates into two distinct categories: aminobisphosphonates, which sensitize macrophages to an inflammatory stimulus inducing an acute-phase response, and non-aminobisphosphonates that can be metabolized into macrophages and that may inhibit the inflammatory response of macrophages. There is evidence of aminobisphosphonate-induced pro-inflammatory response, in particular, related to modifications of the cytokine network. Several in vivo studies have demonstrated an acute-phase reaction after the first administration of aminobisphosphonates, with a significant increase in the main pro-inflammatory cytokines. However, a peculiar aspect concerning the action of non-aminobisphosphonates seems to be an anti-inflammatory activity caused by the inhibition of the release of inflammatory mediators from activated macrophages, such as interleukin (IL)-6, tumor necrosis factor-alpha and IL-1. The inhibition of inflammatory responses is demonstrated in both in vivo and in vitro models. This activity suggests the use of non-aminobisphosphonates in several inflammatory diseases characterized by macrophage-mediated production of acute-phase cytokines, as prevention of erosions in rheumatoid arthritis, and of loosening of joint prostheses, as well as possibly in osteoarthritis, ankylosing spondylitis, myelofibrosis, and hypertrophic pulmonary osteoarthropathy.
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PMID:Bisphosphonate effects in cancer and inflammatory diseases: in vitro and in vivo modulation of cytokine activities. 1524 2


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