Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Zoledronic acid (Zometa, ZOL) and cytotoxic chemotherapy agents have been reported to have synergistic antitumor activities. However, there is limited data on the effects of combination therapies on the development of bone metastasis in animal models of lung cancer. The purpose of this study was to establish a human lung adenocarcinoma cell line with high bone metastatic potential in an immunodeficient mouse model and to evaluate the synergistic inhibitory activity of zoledronate and paclitaxel (P) on bone metastasis in nude mice. A human lung adenocarcinoma cell line with high bone metastatic potential (SPC-A1-BM) was established by 10 rounds of in vivo selection. Cells were inoculated into the cardiac ventricle of NIH-BNX mice, which were treated 8 days later with: ZOL (0.2 mg/kg s.c. twice weekly) alone, P (6.0 mg/kg every week, i.p.) alone, P + ZOL, or vehicle (10 mice per group). Tumor growth was evaluated with bone scans, X-rays and in situ immunohistochemistry. Serum n-telopeptide of type I collagen (NTX) was measured by ELISA. Survival was assessed using the Kaplan-Meier method. Bone scan, radiographic and histological assessments revealed fewer bone metastases in all treatment groups vs. vehicle, with P + ZOL significantly reducing the incidence of bone metastases detected by bone scans (P=0.020) and X-rays (P=0.036). A histological analysis revealed marginal differences in the number of bone metastases between P + ZOL and vehicle (P=0.058). There was a trend towards differences in survival between the groups (P=0.1511) and survival was significantly longer for the P + ZOL group vs. vehicle (P=0.022). Compared with vehicle and ZOL alone, cancerous cells in the bone of mice treated with P + ZOL expressed higher levels of Bax and lower levels of Bcl-2 and Bcl-xl. ZOL produced a trend towards reduced NTX levels vs. vehicle and P + ZOL produced a profound reduction in NTX vs. vehicle (P=0.022). The results of this study indicated that zoledronate enhanced the efficacy of paclitaxel synergistically, by reducing the incidence of bone metastasis from lung cancer and prolonging survival in a mouse model of non-small cell lung cancer with a high potential for metastasis to bone.
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PMID:Synergistic inhibitory activity of zoledronate and paclitaxel on bone metastasis in nude mice. 1869 9

Zoledronic acid is reported to significantly reduce skeletal morbidity and prolong time to bone lesion progression in patients with bone metastases from various malignant tumors including renal cell carcinoma. Due to renal uptake and elimination of zoledronic acid, however, it is difficult to control dose alignment in patients with kidney dysfunction. We reviewed significance of hemodialysis and monitoring of serum creatinine and calcium in patients with ESRD. (Cases) We experienced two cases of end-stage renal disease (ESRD) with bone metastases from advanced renal cell carcinoma. Zoledronic acid was given to both patients by 15 minutes intravenous infusion followed by hemodialysis 24 hours later. Systemic cytokine infusion and oral thalidomide were also given to both patients. Level of serum calcium reduced in one case two weeks later, and treated by calcium administration. No other adverse effects were noted for more than six months of combination therapy. Both cases maintained stable disease not only for bone metastases but also for the systemic condition without any organ failure. Even in patients under maintenance hemodialysis, zoledronic acid can be given with certain safety and efficacy by hemodialysis 24 hours after administration and intense monitoring of serum calcium level. We think this is the first report of zoledronic acid treatment to ESRD patients with bone metastases from malignant tumors.
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PMID:[Zoledronic acid for bone metastases due to advanced renal cell carcinoma under chronic hemodialysis--a report of two cases]. 1869 74

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

Zoledronic acid 4 mg administered as a 15-minute infusion every 3-4 weeks is effective and well tolerated in the treatment of patients with breast cancer metastatic to bone. It is effective in reducing complications arising from metastatic bone disease in this patient population, with a clinical profile that compares favourably with that of pamidronate. Zoledronic acid administered on a less frequent schedule (every 3-6 months) has also shown potential in preventing cancer treatment-induced bone loss in pre- and postmenopausal women with breast cancer receiving adjuvant hormonal therapy. Preliminary data suggest that zoledronic acid may have antitumour effects, which may reduce the risk of overall disease progression in patients with malignant disease. Thus, zoledronic acid has a well established role as first-line treatment in patients with bone metastases secondary to breast cancer, and may prove useful as a preventive treatment for cancer treatment-induced bone loss or an adjuvant therapy in women with breast cancer.
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PMID:Zoledronic acid: a review of its use in breast cancer. 1909 6

Approximately 30 to 40% of patients with advanced lung cancer will develop bone metastases in the course of their disease, resulting in a significant negative impact on both morbidity and survival. Skeletal complications of bone metastases include pain, pathologic fractures, spinal cord compression, and hypercalcemia. Total medical care costs are greater among patients with bone metastases who develop skeletal complications. A randomized phase III trial of the third generation bisphosphonate zoledronic acid has shown clinical benefit in the management of a subgroup of patients with bone metastases from lung cancer. Zoledronic acid treatment was associated with a reduction in both the risk of, and time to, a skeletal-related event. One of the markers of bone resorption, N-telopeptide, is both prognositic for development of skeletal-related events and predictive for benefit from zoledronic acid. In preclinical models, bisphosphonates have also demonstrated antitumor activity and are therefore currently being evaluated in adjuvant trials. Inhibition of the receptor activator of nuclear factor kappa B ligand-RANK pathway can reduce osteoclast-mediated bone resorption, and trials comparing receptor activator of nuclear factor kappa B ligand inhibitors with bisphosphonates are ongoing, including patients with lung cancer. In this article, we review the management of bone metastases and hypercalcemia as well as potential future directions for bone directed therapies in patients with lung cancer.
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PMID:Prevention and management of bone metastases in lung cancer: a review. 1917 5

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

Surgical castration is still considered the 'gold standard' for androgen deprivation therapy which have become the mainstay for the management of advanced prostate cancer. The main drawback of this safe operation is that it may have a negative psychological effect, thus, in recent years, a decline in the utilization of bilateral orchiectomy which is the most cost-effective form of androgen deprivation therapy can be witnessed. Testicular prostheses have been shown to reduce the psychological impact resulting from loss or absence of a testicle in those patients. Besides, patients with advanced prostate cancer are at risk of skeletal complications and bisphosphonates are used in treatment. Zoledronic acid is the only bisphosphonate agent demonstrated to effectively reduce skeletal related events in patients with advanced prostate cancer metastatic to bone. Therefore, zoledronic acid releasing testicular prostheses can be used in the treatment of prostate cancer patients with bone metastases after bilateral orchiectomy. This technology has the potential to become the preferred clinical management tool for prostate cancer patients with bone metasthases after bilateral orchiectomy.
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PMID:Slow zoledronic acid releasing testis prostheses in the treatment of prostate cancer patients with bone metastases. 1940 41

Bone metastases occur in 20-40% of patients with lung cancer. Recent studies demonstrate a direct antiproliferative effect of 3rd generation bisphosphonates (BPs) on lung tumors, which may influence the survival. Therefore, we examined the clinical impact of zoledronic acid (ZOL; Zometa), a 3rd generation BP, with a focus on the survival, time to progression and pain effect in lung cancer patients with bone metastases. Lung cancer patients (n = 144, Stage IV) with evidence of metastasis bone scan were included. Eighty-seven of 144 experienced bone pain and received ZOL, 4 mg i.v. every 21 days (Group A), whereas the other 57 patients received no ZOL (Group B). All patients were treated with a combination chemotherapy consisted of docetaxel 100 mg/m(2) and carboplatin AUC = 6. It was found that Group A had a statistically significant longer survival (p < 0.01) when compared to Group B. A statistically significant positive correlation was found between the number of cycles of therapy with ZOL and total patient survival (p < 0.01, Pearson correlation) and time to progression (p < 0.01). Pain effect of ZOL had no significant difference between the 2 groups of patients (p > 0.05). Urine N-telopeptide of type I collagen (NTx) levels decreased in patients with NTx < or = 29 nM BCE/mM creatinine at baseline after treatment with ZOL. The results of our study suggest that the addition of ZOL increases overall survival in lung cancer patients with bone metastases. The longer period of receiving ZOL, the better effect on survival and time to progression.
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PMID:The impact of zoledronic acid therapy in survival of lung cancer patients with bone metastasis. 1952 84

Lung cancer is one of the most common cancers diagnosed worldwide. As the disease progresses, patients with lung cancer can develop metastasis to the bone. However, because early-stage bone disease may be asymptomatic, bone metastases often go undiagnosed, resulting in delayed initiation of treatment to prevent skeletal complications. In the absence of bone-targeted therapies, patients with metastatic bone disease are at increased risk for potentially debilitating skeletal-related events (SREs) including pathologic fracture, spinal cord compression, hypercalcemia of malignancy, and the requirement for surgery or radiation therapy to bone. The majority of patients with bone metastases from lung cancer will develop SREs, and this number is expected to increase with the improvement of primary therapies that are prolonging the lives of patients. Zoledronic acid is the only bisphosphonate that has been extensively studied in patients with bone metastases from lung cancer, and it has demonstrated efficacy in delaying the onset and reducing the risk of SREs in this setting. Preventing SREs with zoledronic acid may preserve the quality of life and functional independence of these patients. Recent exploratory analyses of a phase III study in patients with bone metastases from lung cancer or other solid tumors revealed that zoledronic acid also normalizes biochemical markers of bone metabolism and may also improve survival in specific patient subsets. Additional ongoing clinical trials are assessing further benefits and antitumor activity of zoledronic acid in the adjuvant setting in the prevention of bone metastases in patients with lung cancer.
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PMID:Skeletal disease contributes substantially to morbidity and mortality in patients with lung cancer. 1963 38


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