Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zoledronic acid is a highly potent bisphosphonate that has been shown to reduce skeletal-related events in patients with androgen-independent prostate cancer metastatic to bone. We report a patient with androgen-independent prostate cancer and extensive bone metastases. After receiving a single dose of zoledronic acid, the patient developed hypocalcemia that persisted for approximately 60 days despite intravenous and oral calcium supplementation, likely because of excess unopposed osteoblastic activity. This case underscores the need for calcium and vitamin D monitoring and supplementation to avoid bisphosphonate-induced secondary hyperparathyroidism and highlights the possibility that extensive osteoblastic metastasis alone might lead to hypocalcemia.
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PMID:Persistent hypocalcemia induced by zoledronic acid in a patient with androgen-independent prostate cancer and extensive bone metastases. 1795 15

Patients with metastatic bone disease are at risk for developing skeletal-related events that can negatively influence quality of life, contributing to loss of autonomy and functional capabilities. Bisphosphonates have become an important component in the treatment of patients with bone metastases as they delay the onset and reduce the risk of skeletal-related events and also palliate or control bone pain in multiple cancer types, thus preserving quality of life. Zoledronic acid has proven efficacy and safety in patients with bone lesions from breast cancer, prostate cancer, lung cancer, and other solid tumors, as well as in patients with multiple myeloma. Current data suggest that early treatment with zoledronic acid (before the onset of bone pain) may provide additional clinical benefits and also positive effects on survival in subsets of patients who have elevated levels of N-telopeptide of type I collagen (NTX), a biochemical marker of bone resorption. Studies have shown that in patients with breast cancer, prostate cancer, lung cancer, or other solid tumors, normalization of elevated levels of NTX was observed in the majority of patients who received zoledronic acid. Furthermore, normalization of NTX values correlated with extended survival.
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PMID:Clinical benefits and considerations of bisphosphonate treatment in metastatic bone disease. 1806 86

Zoledronic acid (Zometa is a third-generation nitrogen-containing parenteral bisphosphonate indicated for the treatment of bone metastases due to solid tumours or multiple myeloma and for hypercalcaemia of malignancy (HCM). In patients with advanced breast or prostate cancer, zoledronic acid 4 mg every 3-4 weeks for up to 15 months significantly reduced the proportion of patients with > or =1 skeletal-related event (SRE), excluding HCM, compared with placebo. In patients with advanced breast cancer or multiple myeloma, the incidence of SREs was similar in patients treated with zoledronic acid 4 mg or pamidronic acid 90 mg every 3-4 weeks for up to 25 months but, in breast cancer patients, zoledronic acid reduced the risk of SREs, including HCM, by an additional 20% compared with pamidronic acid. In modelled cost-utility studies comparing direct costs based on efficacy and resource-use data from these and/or other trials, results have varied. In the most recent study performed from the perspective of the UK NHS and modelled over a 10-year treatment period in women with advanced breast cancer, intravenous zoledronic acid and oral ibandronic acid were dominant over no treatment. Intravenous zoledronic acid was the most cost effective, in terms of incremental costs per QALY gained, followed by oral ibandronic acid, intravenous pamidronic acid and intravenous ibandronic acid. Two other modelled analyses in patients with advanced breast cancer, also conducted from the perspective of the NHS, evaluated the cost utility of three bisphosphonate therapies in patients receiving hormonal therapy or intravenous chemotherapy. Analyses were modelled over 14.3 months (i.e. expected survival) and assumptions varied markedly from results in clinical breast cancer trials. Also, efficacy assumptions for zoledronic acid were not based on clinical trials with the drug. The results of these analyses suggest that oral ibandronic acid is more cost effective than intravenous zoledronic acid and intravenous pamidronic acid in terms of incremental cost per QALY gained. In a global, 15-month modelled cost-effectiveness analysis of patients with advanced prostate cancer, conducted from a third-party perspective, the incremental cost per QALY gained for zoledronic acid versus no treatment was $US159 200 (year 2000 value), which is about 3-fold greater than commonly accepted thresholds for cost effectiveness. In conclusion, a recent modelled economic analysis suggests that intravenous zoledronic acid 4 mg is dominant relative to no treatment in the management of bone metastases in patients with advanced breast cancer. In contrast, in patients with advanced prostate cancer, the incremental cost per QALY gained for zoledronic acid 4 mg versus no treatment was predicted to be higher than commonly accepted thresholds. Compared with other bisphosphonates in the setting of advanced breast cancer, intravenous zoledronic acid was more cost effective than oral or intravenous ibandronic acid and intravenous pamidronic acid in one study, but less cost effective than oral ibandronic acid in another. Further efficacy and economic data comparing intravenous zoledronic acid with oral ibandronic acid are needed. Meanwhile, zoledronic acid appears to be the most cost effective intravenous bisphosphonate for the management of bone metastases in patients with advanced breast cancer and possibly in patients with different types of advanced solid tumours.
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PMID:Zoledronic acid: a pharmacoeconomic review of its use in the management of bone metastases. 1828 18

Macrophages are considered a key component of the immunosuppressive environment present in solid tumors, where they support tumor growth through the production of pro-angiogenic factors and active suppression of effector immune responses. Zoledronic acid (ZA), an aminobisphosphonate clinically approved for treatment of symptomatic skeletal events, has recently been shown to have immunomodulatory properties that can be exploited in cancer immunotherapy. Here, we utilize an in vitro model of prostate cancer cell-macrophage interaction to dissect the effect of ZA, on the function of prostate cancer tumor-associated macrophages (PC-TAM). We show that prostate cancer cells recruit macrophages, which in turn express a variety of proangiogenic and immunosuppressive mediators. ZA selectively suppressed the expression of MMP-9 by PC-TAM, whereas the expression of other mediators was not limited. PC-TAM treated with ZA, on the other hand, could effectively drive the proliferation of activated Tgammadelta lymphocytes, which lysed bisphosphonate-pulsed prostate cancer cells. Moreover, ZA boosted the production of type-1 cytokines by PC-TAM in response to immunomodulators such as IL-12 and polyI:C, which are known to polarize macrophages towards an anti-tumoral M1 phenotype. Overall, we provide evidence that ZA shifts the balance of PC-TAM from a tumor promoting to a tumor-eliminating phenotype and also suggest a potential use of this pharmacological agent as an immunotherapeutic adjuvant.
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PMID:Zoledronic acid modulates antitumoral responses of prostate cancer-tumor associated macrophages. 1829 80

Zoledronic acid (Zometa), a third-generation amino-bisphosphonate, has been approved in the US, the EU and many other countries worldwide for the prevention of skeletal-related events in patients with bone metastases of malignancy. In several well designed trials, zoledronic acid 4 mg administered as a 15-minute infusion every 3-4 weeks was effective in reducing the occurrence of skeletal complications in patients with bone metastases secondary to multiple myeloma, breast cancer or prostate cancer. Zoledronic acid was as effective as pamidronic acid in reducing the occurrence of skeletal complications in patients with multiple myeloma or breast cancer. In patients with solid tumours other than breast or prostate cancer, zoledronic acid did not show significant clinical benefit over placebo in terms of the primary endpoint; however, some benefit of therapy in terms of secondary endpoints was observed with zoledronic acid relative to placebo. Its efficacy in a broad range of tumours and short infusion time (15 minutes) are an advantage over other available bisphosphonates. Modelled pharmacoeconomic analyses in patients with breast cancer suggested that zoledronic acid therapy is cost effective relative to no therapy with regard to the cost per quality-adjusted life-year (QALY) gained; however, results were mixed when zoledronic acid was compared with other commonly used bisphosphonates. Zoledronic acid is generally well tolerated; the risk of osteonecrosis of the jaw may be minimized by adhering to recommendations regarding dental therapy. Additional efficacy and economic data are required to definitively position zoledronic acid with respect to other bisphosphonates. Nevertheless, available clinical data indicate that zoledronic acid is an effective treatment option for the management of bone metastases of malignancy.
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PMID:Zoledronic acid : a review of its use in the management of bone metastases of malignancy. 1831 68

Zoledronic acid (Zometa, Novartis, Basel, Switzerland) is a new generation of bisphosphonates (BPs) with demonstrated clinical benefit in breast and prostate cancer patients with bone metastases. The safety and efficacy of intravenous zoledronic acid in lung cancer patients was assessed. In 86 patients with newly diagnosed non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) and bone metastases, 4 mg of zoledronic acid was administered with rapid 15-minute intravenous infusion every 3-4 weeks. A total of 414 infusions were administered over a 24-month period during which a statistically significant decrease in serum calcium levels (p = 0.03) was observed. Serum alkaline phosphatase (ALP) also decreased but not significantly. With regard to clinical efficacy, 55 of our patients stabilized or reduced their need for analgesic treatment. No significant side-effects, including fever, hemodynamic instability and renal dysfunction, were seen. We conclude that the rapid infusion of zoledronic acid is safe and convenient for lung cancer patients even after the 3rd and 6th months follow-up.
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PMID:Safety and efficacy of zoledronic acid rapid infusion in lung cancer patients with bone metastases: a single institution experience. 1838 97

Bone metastases are a major cause of morbidity for men with prostate cancer. Although typical bone metastases from prostate cancer appear osteoblastic by radiographic imaging, excess number and activity of both osteoblasts and osteoclasts characterize most "osteoblastic" bone metastases. Additionally, pathological osteoclast activation is associated with increased risk of skeletal complications, disease progression, and death. Zoledronic acid, a potent intravenous bisphosphonate, reduces markers of osteoclast activity and significantly decreases the risk of skeletal complications in men with androgen-independent prostate cancer and bone metastases. Additional studies are needed to determine the optimal timing, schedule, and duration of bisphosphonate treatment in men with bone metastases as well as the potential role of bisphosphonates in other settings, including the prevention of bone metastases. Denosumab is a human monoclonal antibody that binds and neutralizes human receptor activator of NF-kappaB ligand (RANKL), a critical mediator of osteoclast activation, differentiation, and survival. Three ongoing pivotal studies involving more than 4,500 subjects will evaluate the role of denosumab for prevention of treatment-related fractures, bone metastases, and disease-related skeletal complications in men with prostate cancer.
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PMID:Osteoclast targeted therapy for prostate cancer: bisphosphonates and beyond. 1859 21

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

The patient was a 63-year-old man who had a recurrence and bone metastasis of prostate cancer after total prostatectomy. He was diagnosed with prostate cancer refractory to hormones. Subsequently, the PSA level decreased after docetaxel therapy, but then gradually increased. Thus, he was diagnosed with bone metastasis of prostate cancer refractory to therapy with hormones or docetaxel. The PSA level decreased after the start of therapy with docetaxel+ zoledronic acid. Zoledronic acid seems to be effective not only for the prevention but also for the treatment of skeletal related events(SRE)in patients with prostate cancer with bone metastases.
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PMID:[A case of hormone/docetaxel-refractory prostate cancer in which PSA level decreased after docetaxel+zoledronic acid treatment]. 1863 74


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