乳腺癌辅助治疗.ppt

* Abstract To determine whether zoledronic acid (ZA) can prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer. In this randomized, open-label, phase III multicenter trial, premenopausal women[40 years were randomly assigned to ZA treatment (4 mg IV, every 6 months) or observation after surgery. All patients were treated with four cycles of AC followed by four cycles of taxane. Between March 2007 and May 2008, we assessed a total of 112 premenopausal women, all of whom developed amenorrhea at 1 year after chemotherapy. The mean percent change of BMD in the lumbar spine (LS) was -1.1% in the ZA group versus -7.5% in observation group at 12 months. Differences in percent change of BMD from baseline between the two groups were 6.4% for the LS, and 3.6% for the femoral neck. The mean levels of bone turnover at 12 months were significantly lower in the ZA group. ZA was generally well tolerated. Infusion of ZA 4 mg every 6 months effectively prevented bone loss within the first year in premenopausal women receiving adjuvant chemotherapy for early breast cancer. Regular BMD measurements and early bisphosphonate therapy should be considered in these patients. * * * * * * * Zoledronic acid (ZOL) and other nitrogen-containing bisphosphonates (NBPs) are potent inhibitors of the enzyme farnesyl pyrophosphate (FPP) synthase, a key enzyme in the mevalonate pathway.1,2 Some of the downstream products of the mevalonate pathway are the lipids FPP and geranylgeranyl pyrophosphate (GGPP).1,2 These lipids are added to small GTP-binding proteins, such as Rho and Ras, during protein prenylation and are essential for the proper localization and activity of these proteins.1,2 Inhibition of FPP synthase by ZOL therefore disrupts the production of FPP and GGPP and the prenylation of Rho and Ras, resulting in suppression of osteoclast function and survival.1,2 In addition, inhibition of FPP synthase leads to accumulation of upstream intermediates, such a