Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.8 (FAST)
 758 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zoledronic acid, a nitrogen-containing bisphosphonate, is firmly established in the management of metastatic bone disease. It inhibits farnesyl diphosphonate synthase within the mevalonate pathway and, through this mechanism, is a potent inhibitor of osteoclast-mediated bone resorption. In addition, there are preclinical data suggesting that farnesyl diphosphonate synthase inhibition by zoledronic acid has anti-tumor effects in breast cancer. Adjuvant therapies for early breast cancer are associated with substantial decreases in bone mineral density. Results from three clinical trials, ABCSG-12, Z-FAST and ZO-FAST, indicate that the addition of twice-yearly zoledronic acid to standard adjuvant endocrine therapy in premenopausal and postmenopausal patients with hormone receptor-positive breast cancer prevents cancer treatment-induced bone loss. Moreover, it is becoming evident that it may also exert anticancer effects in an estrogen-deprived state in the adjuvant and neoadjuvant setting. However, long-term side effects need to be taken into consideration for treatment decisions.
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PMID:Zoledronic acid for adjuvant use in patients with breast cancer. 2141 49

Aromatase inhibitor-associated bone loss has not been proved in the Japanese or Asian women. The aim of this study was to evaluate an upfront or delayed strategy of bone protection therapy with zoledronic acid administered at 4 mg every 6 months in postmenopausal Japanese women with early breast cancer to compare with results of the Z-FAST and ZO-FAST studies in western countries. Postmenopausal women with hormone receptor positive early breast cancer receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months). The delayed group received zoledronic acid when lumbar spine (L(2)-L(4)) bone mineral density (BMD) decreased to less than young adult mean -2.0SD or when a nontraumatic fracture occurred. The primary endpoint of this study was to compare the percent change in L(1)-L(4) BMD at 12 months between the groups. Secondary endpoints included percent changes in L(2)-L(4) and total hip (TH) BMD. The upfront and delayed groups included 94 and 95 patients, respectively. At 12 months, L(1)-L(4), L(2)-L(4), and TH BMD significantly decreased by 2.0, 2.4, and 2.4%, respectively, in the delayed group. L(1)-L(4) BMD was 4.9% higher in the upfront group than in the delayed group (95% CI 3.9-5.8%; p < 0.001). L(2)-L(4) BMD was 5.6% higher (95% CI 4.5-6.6%; p < 0.001), and TH BMD was 4.4% higher (95% CI 3.3-5.4%; p < 0.001). At 12 months, upfront zoledronic acid therapy prevented bone loss in postmenopausal Japanese women who were receiving adjuvant letrozole, confirming the Z-/ZO-FAST study results in western populations.
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PMID:Efficacy of zoledronic acid in postmenopausal Japanese women with early breast cancer receiving adjuvant letrozole: 12-month results. 2230 66