Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zoledronic acid (ZA) delays the onset or reduces the incidence of skeletal complications in breast cancer patients with bone metastases. However, there are few data on the long-term renal safety of ZA. We retrospectively evaluated 43 breast cancer patients with bone metastases who received ZA more than 24 months. The following parameters measured prior to first ZA use and after the last dose of ZA administration were compared: serum creatinine (SCr), blood urea nitrogen (BUN), alkaline phosphatase (ALP), calcium (Ca), and phosphorous (P). Forty-three breast cancer patients with documented bone metastases were evaluated. Median age at the start of treatment was 53 years (range 37-77). Median overall duration of ZA administration was 36 months (25-62). There were no statistically significant differences in the pre- and post-treatment levels of SCr, BUN, Ca and P. However, ALP levels after long-term ZA administration were decreased significantly (P<0.05). More than 24 months of ZA administration did not adversely affect the renal function. ZA can be used safely in breast cancer patients with bone metastases beyond 2 years.
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PMID:Renal safety of zoledronic acid administration beyond 24 months in breast cancer patients with bone metastases. 1819 80

In this study we have investigated changes in circulating angiogenic factors after a single zoledronic acid intravenous infusion. Thirty consecutive patients who had histologically confirmed breast (n=20) and lung cancer (n=10) associated with confirmation of bone metastases were included in the study. Serum was also available from 10 healthy volunteers. Four mg of Zoledronic acid (Zometa, Novartis) was administered as a 15-min infusion in 100-ml normal saline on an outpatient basis. Venous blood for assessment of serum parameters was drawn just before the beginning of drug infusion and again at 7 and 28 days after the zoledronic acid infusion. Serum levels of VEGF and bFGF were assayed with ELISA kits. Serum VEGF and bFGF levels were not significantly different from healthy control groups (P>0.05). However, we found that serum VEGF levels in lung cancer patients were significantly higher than in patients with breast cancer and controls (P=0.009, and P=0.022, respectively). We found no significant correlation between serum VEGF and bFGF levels. No statistically significant changes were seen following infusion of zoledronic acid in patients with bone metastases for both serum VEGF and bFGF levels (P>0.05). Unlike previous studies, zoledronic acid did not appear to exert an angiogenic activity as there was no reduction of VEGF and bFGF circulating levels after zoledronic acid infusion.
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PMID:Effect of zoledronic acid on serum angiogenic factors in patients with bone metastases. 1820 21

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

V gamma 9 V delta 2 T cells exert potent cytotoxicity toward various tumor cells and adoptive transfer of V gamma 9 V delta 2 T cells is an attractive proposition for cell based immunotherapy. V gamma 9 V delta 2 T cells expanded in the presence of Zoledronate and IL-2 express CD16 (Fc gamma RIII), which raises the possibility that V gamma 9 V delta 2 T cells could be used in conjunction with tumor targeting monoclonal antibody drugs to increase antitumor cytotoxicity by antibody dependent cellular cytotoxicity (ADCC). Cytotoxic activity against CD20-positive B lineage lymphoma or chronic lymphocytic leukemia (CLL) and HER2-positive breast cancer cells was assessed in the presence of rituximab and trastuzumab, respectively. Cytotoxicity of V gamma 9 V delta 2 T cells against CD20-positive targets was higher when used in combination with rituximab. Similarly, V gamma 9 V delta 2 T cells used in combination with trastuzumab resulted in greater cytotoxicity against HER2-positive cells in comparison with either agent alone and this effect was restricted to the CD16(+)V gamma 9 V delta 2 T cell population. Our results show that CD16(+)V gamma 9 V delta 2 T cells recognize monoclonal antibody coated tumor cells via CD16 and exert ADCC similar to that observed with NK cells, even when target cells are relatively resistant to monoclonal antibodies or V gamma 9 V delta 2 T cells alone. Combination therapy involving ex vivo expanded CD16(+)V gamma 9 V delta 2 T cells and monoclonal antibodies may enhance the clinical outcomes for patients treated with monoclonal antibody therapy.
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PMID:V gamma 9 V delta 2 T cell cytotoxicity against tumor cells is enhanced by monoclonal antibody drugs--rituximab and trastuzumab. 1830 55

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

Persistent circadian rhythm of bone turnover in bone metastatic breast cancer suggests greater skeletal retention of bisphosphonates if administered in the night. We assessed differential effects of night vs morning administration of zoledronic acid (ZA) on bone turnover. Forty-four breast cancer patients with bone metastases were randomised to receive intravenous ZA (4 mg) at 1100 or 2300 hours every 28 days for four times. Urinary concentration N-telopeptide of type-I collagen (NTX) and deoxypyridinolines, and serum C-telopeptide of type-I collagen (CTX), bone alkaline phosphatase (ALP), osteocalcin and Parathyroid hormone (PTH) was measured in the morning at baseline and after 4, 7, 14, 28, 56 and 84 days. Urinary ZA concentration was also measured. Zoledronic acid caused significant decreases of NTX and CTX (P<0.001), without any difference in percent changes between night and morning arms. Bone ALP and osteocalcin were also significantly affected by ZA (P=0.001), without any difference between arms. Parathyroid hormone significantly increased in both the arms; PTH increase was lower in the night arm (P=0.001). From the second administration onwards, urinary ZA level was significantly higher in the night arm (P<0.01). Administration of ZA at two opposite phases of the circadian cycle causes similar changes of bone-turnover marker levels, but has differential effects on the level of serum PTH.
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PMID:Changes of bone turnover markers and serum PTH after night or morning administration of zoledronic acid in breast cancer patients with bone metastases. 1850 77

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

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

The American Society for Clinical Oncology (ASCO) determined that there were twelve major advances in medical oncology last year. Endocrine-responsive breast cancer benefits from tamoxifen or an aromatase inhibitor taken for more than five years. Zoledronic acid, a bisphosphonate, reduces the risk of breast cancer recurrence in premenopausal women undergoing hormonal-suppression therapy. Bevacizumab was for use in combination with paclitaxel in patients with metastatic breast cancer Cetuximab added to chemotherapy of non-small cell lung cancer patients increased survival by up to 21%. Adjuvant gemcitabine doubled disease-free survival in pancreas cancer. Adjuvant pegylated interferon cuts the risk of recurrent melanoma by 18%. Bendamustine abolishes signs of activity of chronic lymphocytic leukemia in 30% of patients. The HPV vaccine--now approved for prevention of cervical cancer--might have a role in preventing oral cancers and a review of 45 studies showed that oral contraceptives reduce the risk of ovarian cancer.
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PMID:[Oncology]. 1927 50

PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.
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PMID:Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial. 2008 30


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