唑来膦酸（Zoledronic acid）对乳癌的预后有助益发表於NEJM的资料：Zoledronic Acid有益於乳癌
一项刊载於1月12日新英格兰医学期刊的研究显示，zolendronic acid对乳癌的预后有助益。
这是首次显示用於骨质疏鬆和骨骼转移的双磷酸盐也对乳癌有帮助的研究，初步结果发表於去年的美国临床肿瘤学会(ASCO)会议中，Medscape Oncology当时也有报导。
这项发现来自「Austrian Breast and Colorectal Cancer Study Group (ABSCG)-12」 试验，第一作者是奥地利维也纳医学大学的Michael Gnant医师，此研究由行销anastrozole(商品名Arimidex)的阿斯特捷利康药厂与行销zoledronic acid(商品名Zometa或Reclast)的诺华药厂所资助。
试验包括1,803名有雌激素反应早期乳癌之停经前妇女，手术之后，她们接受标準治疗，包括使用goserelin加上以tamoxifen或芳香胺酶抑制剂anastrozole辅助内分泌治疗之卵巢抑制治疗3年，显示tamoxifen组和anastrozole组之间的结果没有差异。
此外，半数妇女被随机指派接受每6个月一次的zoledronic acid 4 mg，也是为期3年。
加入zoledronic acid显著改善了无疾病存活，获得3.2%的绝对降低与36%的疾病恶化改善(风险比[HR])为0.64；95%信心区间[CI])为0.46-0.91；P=.01)。
不过，zoledronic acid并未改善整体存活，它未显著降低死亡风险(HR，0.60；95% CI，0.32-1.11；P= .11)。
【这些结果会改变实务吗？】
Gnant医师等人表示，本试验的资料显示，使用内分泌治疗进行卵巢抑制3年，对於低到中度风险者可以產生相当好的结果。
他们也认为，加入zoledronic acid的好处和其他试验结果一样，在过去，已经导致治疗标準的变化。
Zoledronic acid组的治疗意向世代分析中，每达到1位治疗或预防疾病恶化的数量为31人，平均追踪47.8个月。
相对的，早期乳癌之停经妇女的taxane化疗的后设分析发现，使用paclitaxel者每达到1位治疗或预防疾病恶化的数量为28人(平均追踪60–69个月)，使用docetaxel者每达到1位治疗或预防疾病恶化的数量为31人(平均追踪43–60 个月)。
此外，研究者指出，在之前的研究中，zoledronic acid已经显示可预防芳香胺酶抑制剂引起的骨质流失。
在去年的ASCO会议中，Gnant医师认为，应考量使用zoledronic acid的辅助治疗，以改善停经前乳癌病患的照护标準。
会中讨论结果时，哈佛医学院的Eric Winer医师与纽约市威尔康乃尔医学院的Linda Vahdat医师同意现在应将zoledronic acid视为适当的治疗。
不过，法国Jules Bordet研究中心的Martine Piccart-Gebhart医师表示，这些结果尚未改变实务。她表示，在提出常规使用此药的建议之前，需要其他试验确认。
【更多研究显示Zoledronic Acid有好处】
自此之后，越来越多研究报告认为zoledronic acid对於乳癌有好处，虽然是用於不同的病患族群。2008年12月圣安东尼奥乳癌研讨会中发表了两篇研究，Medscape Oncology当时也有报导。
一组结果来自AZURE (Neo-Adjuvant Zoledronic Acid to Reduce Recurrence)试验，研究对象是3,360名第2或3期乳癌病患，包括了停经前和停经后妇女，其中205名妇女的回溯病理分析初步资料显示，当在手术前给予zoledronic acid作为化疗之新的协同辅助治疗时，肿瘤大小缩减相当多，获得较少的转移。
另一组结果来自ZO-FAST (Zometa-Femara Adjuvant Synergy Trial)，显示zoledronic acid可以预防早期乳癌之停经后妇女使用芳香胺酶抑制剂letrozole (Femara，诺华药厂)有关的骨质流失；试验也显示，整个3年研究期间都服用zolendronic acid的妇女，乳癌復发率显著降低。
主要作者、德国Frauenklinik大学的Holger Eidtmann医师被问到他是否会建议使用zoledronic acid於復发风险增加的乳癌病患时，他表示不会，他认为下此结论的时机尚早；这些结果只有3年的追踪资料。
但是他相信，zolendronic acid对於乳癌有抗肿瘤活性。
阿斯特捷利康和诺华药厂支持ABCSG-12 研究；诺华药厂支持AZURE研究和ZO-FAST研究。Gnant医师以及多位ABSCG-12 作者报告与多家药厂的不同关係，包括接受阿斯特捷利康药厂和诺华药厂的顾问费用与研究资金。详见报告。
Zoledronic Acid Benefit in Breast Cancer:
Data Published in NEJM Details of a study showing a beneficial effect ofzolendronic acid on breast cancer outcomes are published in the February 12 issue of the New England Journal of Medicine.
This was one of the first studies to show that the drug, a bisphosphonate used for osteoporosis and bone metastases, also has a benefit in breast cancer. Preliminary results were presented at the American Society of Clinical Oncology (ASCO) meeting last year, and reported by Medscape Oncology at the time.
The finding comes from the Austrian Breast and Colorectal Cancer Study Group (ABSCG)-12 trial, and the first author isMichael Gnant, MD, from the Medical University of Vienna, in Austria. The study was funded by AstraZeneca, which markets anastrozole (Arimidex), and Novartis, which markets zoledronic acid (Zometa, Reclast).
The trial involved 1803 premenopausal women with estrogen-responsive early breast cancer. After surgery, theyreceivedstandard treatment, comprised of ovarian suppression with goserelin plus adjuvant endocrine treatment with either tamoxifen or the aromatase inhibitor anastrozole for a period of 3 years. The results showed no difference in the outcomes between tamoxifen and anastrozole groups.
In addition, half of the women were randomized to receive zoledronic acid 4?mg intravenously every 6 months, also for 3 years.
The addition of zoledronic acid significantly improved disease-free survival. It resulted in an absolute reduction of 3.2% and a relative reduction of 36% in the risk for disease progression (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.46 to 0.91; P?= .01).
However, zoledronic acid did not improve overall survival. It did not significantly reduce the risk for death (HR, 0.60; 95% CI, 0.32 to 1.11; P?= .11).
Are Results Practice-Changing?
Dr. Gnant and colleagues say the data from this trial show that ovarian suppression with endocrine therapy for 3 years \"can produce excellent outcomes\" in a population with low to intermediate risk.
They also suggest that the benefit seen from adding zoledronic acid is of the same order as results that, \"in the past, have caused a shift in treatment standards.\"
The estimated number needed to treat to prevent disease progression in 1 patient in the intention-to-treat cohort was 31 in the zolendronic-acid group at median follow-up of 47.8 months.
In contrast, a meta-analysis of taxane chemotherapy in postmenopausal women with early breast cancer found the number needed to treat to prevent disease progression in 1 patient was 28 with paclitaxel (with a median follow-up of 60–69 months) and 31 with docetaxel (with a median follow-up of 43–60 months).
In addition, the researchers point out that zoledronic acid has been shown in previous studies to prevent the bone loss caused by aromatase inhibitors.
At the ASCO meeting last year, Dr. Gnant suggested that \"adjuvant treatment with zoledronic acid should be considered in order to improve the standard of care in premenopausal breast cancer patients.\"
Discussing the results at the meeting, Eric Winer, MD, from Harvard Medical School, in Boston, Massachusetts, and Linda Vahdat, MD, from Weill Cornell Medical College, in New York City, agreed that zoledronic acid should now be considered an appropriate therapy.
However, Martine Piccart-Gebhart, MD, PhD, from the Institut Jules Bordet, in Paris, France, said these results \"are not practice-changing — not yet.\" She said that there is a need for confirmation from other trials before the drug can be recommended for routine care.
More Results Suggesting Benefit for Zoledronic Acid
Since then, more results suggesting a benefit from zoledronic acid in breast cancer have been reported, although in different patient populations. Two studies were presented at the San Antonio Breast Cancer Symposium in December 2008, and werereported at the time by Medscape Oncology.
One set of results come from the AZURE (Neo-Adjuvant Zoledronic Acid to Reduce Recurrence) trial, conducted in 3360 patients with stage?2 or 3 breast cancer, both preandpostmenopausal.Preliminarydatafromasubgroupof205womenforwhomaretrospective pathology analysis had been performed suggest that, when given before surgery, neoadjuvantzoledronicacidworkedsynergistically with chemotherapy and resulted in a greater shrinkage of the tumor, leading to fewer mastectomies.
The other set of results come from ZO-FAST (Zometa-Femara Adjuvant Synergy Trial), which showed that zoledronicacidcanprevent bone loss associated with the aromatase inhibitor letrozole (Femara, Novartis) in postmenopausal women withearlybreastcancer. However, they also show that women who took zolendronic acid throughout the 3-year study had significantly lower breastcancer recurrence.
When the lead researcher, Holger Eidtmann, MD, from the University
Frauenklinik, in Kiel, Germany, was asked whether he would recommend zoledronic acid for breast cancer patients who are at increased risk for relapse, he said: \"No, I think it is too early for that; these results are only 3-year follow-up[data].\"\"But I do believe that there is antitumor activity of zolendronic acid in breast cancer,\" he added.
The ABCSG-12 study was supported by AstraZeneca and Novartis. Both the AZURE and ZO-FAST studies were supported by Novartis. Dr. Gnant and several of the other ABSCG-12 authors report a number ofrelationshipswithvariouspharmaceutical companies, including consultancy and research grants from AstraZeneca and Novartis. Full details appear in the paper.
唑来膦酸的毒副作用
唑来膦酸（Zoledronic acid）
【别名】Zometa。
【作用机制】本品通过抑制破骨细胞的异常活性，使晚期癌症病人严重升高的血钙浓度正常化。
【适应症】用于肿瘤引起的高钙血症。
【不良反应】常见的不良反应为发热，常见的有各类血细胞减少、精神错乱、疲劳、恶心关节痛、味觉倒错、心动过缓、口渴、肌酐升高、低钙血症、低磷盐血症、潜在癌恶化、便秘、呼吸困难等。
【注意事项】孕妇和哺乳期的妇女禁用；用药期间要定期检测血清钙、磷酸盐和镁的水平；与氨基酸苷类合用须谨慎。
提供南京的，成都等多个厂家的的唑来膦酸注射液
国产特价最低的650元一支，进口的2600元，电话022-84277462
全国购买咨询以下单位：
天津市光华医院肿瘤治疗中心购买咨询：022-84277462
辽宁省大连中医药学会春园中西医结合门诊肿瘤门诊购买咨询：0411-83788633