Aranesp对于非化学治疗引起的贫血无效

　　January 29, 2007 — 一项大型、随机分派、安慰剂控制试验已经显示，darbepoetin alfa（Aranesp）使用于癌症病患并不能治疗非因化学治疗引起的贫血，该试验结果也显示，接受该药物治疗的病患死亡率较高；Amgen公司全球发展资深副总裁与医疗事务法人主席Sean Harper医师在一项发给健康照护专业人员的信件中强调，Aranesp并未核准使用于这种情况，而是核准使用于接受化学疗法治疗癌症所造成的贫血，并非癌症本身造成的贫血。
　　
　　Harper医师表示，在这个被设计扩展该药物新适应症的研究中，有时候是非核准适应症，结果并无法减少降低输血的试验终点；该试验并未设计以检验该药物对于存活率的影响，而是要检验安全性终点；然而，相较于接受安慰剂病患，使用Aranesp的病患死亡人数更多。
　　
　　美国食品药物管理局的回覆已经张贴在MedWatch上，该官方组织的安全性资讯与不良反应通报系统网站，该产品的警示为该药物无法降低红血球输注需求，也不能减少疲倦的情况。
　　
　　Darbepoetin alfa被核准使用于非骨髓恶性癌症接受化学疗法引起的贫血，以及使用于慢性肾衰竭的贫血病患，该药物于2001年先被核准使用于肾衰竭病患，接着在2002年被核准使用于癌症病患，该产品是一种红血球生成素，一种由肾脏制造且透过血液循环至骨髓的醣蛋白，在骨髓可以刺激红血球生成。
　　
　　在这一项最新的研究中，darbepoetin alfa相较于使用安慰剂，针对活性癌症不论其是否接受化学治疗或放射线治疗病患；Amgen公司赞助该试验，为一项双盲第三期临床试验，收纳989位血红素低于11 g/dl且罹患癌症病患，由独立的安全性检验委员会监视，将近60%病患罹患活性疾病，使用darbepoetin alfa的目标血红素值为12 g/dl。
　　
　　【增加死亡率且无法减少红血球输注需求与改善疲倦】
　　在最后分析起初16周的结果后，发现该药物对于主要试验终点并无显著影响，使用安慰剂组接受红血球输注的比例为24%，相较于使用治疗组则是18%（P＝.15；危险比例为0.89；95% CI为0.65－1.22）。
　　
　　Darbepoetin alfa治疗组的死亡率比安慰剂组高（26%相较于20%），平均存活追踪时间为4.3个月；使用darbepoetin alfa治疗组实际的死亡数目较高（49%相较于46%；危险比例为1.25；95% CI为1.04－1.51），后续追踪存活时间至少需2年以上。
　　
　　这封给健康照护相关人员的信件中表示，darbepoetin alfa仅供使用于该产品被核准的项目，该公司被要求必须提供相关谘询，请联络Amgen，电话为1-800-77AMGEN（美国）或上网站http://www.amgenmedinfo.com。

Aranesp Ineffective in Anemia Not Caused by Chemotherapy

By Allison Gandey
Medscape Medical News

January 29, 2007 ??A large, multicenter, randomized, placebo-controlled study has shown that darbepoetin alfa, marketed as Aranesp, failed in cancer patients who have anemia not caused by chemotherapy. The study also showed higher mortality in patients who received the product. "Aranesp is not approved for use in this population," Sean Harper, MD, senior vice president of global development and corporate chief medical officer at Amgen, emphasized in a letter to healthcare professionals. "Aranesp is approved for the treatment of patients with anemia that is caused by chemotherapy treatment of their malignant disease, rather than the underlying malignant disease itself."

The study, which was designed to establish the product in this new indication ??sometimes used off-label for this purpose ??failed to meet its primary end point of reducing red blood cell transfusions. "This study was not optimal in design to establish the effect on survival, a safety end point; however, more deaths occurred in the Aranesp treatment group when compared with the placebo group," Dr. Harper reported.

In response, the US Food and Drug Administration has posted an alert on MedWatch, its safety information and adverse-event reporting program. The alert flags the product's ineffectiveness in reducing red blood cell transfusions and adds that it failed to reduce fatigue as well.

Darbepoetin alfa is indicated for the treatment of chemotherapy-induced anemia in patients with nonmyeloid malignancies and for the treatment of anemia associated with chronic renal failure. First approved in 2001 for its renal indication and then in 2002 for cancer patients, the product is an erythropoietic protein. It is said to work in a similar fashion as the body? natural erythropoietin ??a glycoprotein produced by the kidneys that circulates through the bloodstream to bone marrow, where it stimulates red blood cell production.

In this latest study, darbepoetin alfa was compared with placebo in patients with active malignant disease not receiving or expected to receive chemotherapy or radiation therapy. The Amgen-sponsored study was a double-blind phase 3 trial involving a total of 989 patients with a hemoglobin < 11 g/dL with active cancer and was monitored by an independent data safety monitoring board. Approximately 60% of patients had advanced disease. The target hemoglobin in the darbepoetin alfa treatment group was 12 g/dL.

Increased Mortality Observed and Fails to Reduce Red Blood Cell Transfusions or Fatigue

The final analysis of the initial 16-week treatment period did not show a statistically significant effect on the primary efficacy end point, with an incidence of red blood cell transfusions of 24% in the placebo group vs 18% in the treatment group (P = .15; hazard ratio, 0.89; 95% CI, 0.65 ??1.22) .

More deaths were reported in the darbepoetin alfa treatment group than the placebo group (26% vs 20%), with median survival follow-up of 4.3 months. The absolute number of deaths was greater in the darbepoetin alfa treatment group (49% vs 46%; hazard ratio, 1.25; 95% CI, 1.04 ??1.51). Survival follow-up will continue for a minimum of 2 years.

The letter to healthcare professionals points out that darbepoetin alfa should be used only in accordance with its approved product labeling. The company is asking that any questions or requests for additional information be directed to Amgen at 1-800-77AMGEN or http://www.amgenmedinfo.com.