——阿比特龙乙酸酯片-美FDA批准Zytiga用于治疗晚期前列腺癌

近日，美国食品和药物管理局批准了Zytiga（阿比特龙醋酸盐）与强的松（类固醇）联合用于治疗晚期（转移）去势抵抗前列腺癌患者，这些患者先前已经接受过多西他赛化疗。

对于前列腺癌患者，男性荷尔蒙睾丸激素刺激前列腺肿瘤的生长。药物或手术治疗用来减少睾丸激素的生成或者阻止睾丸激素的作用。但是，有时即使睾丸激素水平较低，前列腺癌也可以继续增长。

Zytiga是一种靶向细胞色素P450 17A1（CYP17A1）的药丸，细胞色素P450 17A1在睾丸激素的生成中起重要作用。该药物通过减少这种刺激癌细胞继续生长的激素的生成而起作用。

该申请是经FDA的优先审核程序审核的。Zytiga在监管目标日期2011年6月20日之前被批准。

FDA药物评价和研究中心肿瘤药品办事处主任Richard Pazdur博士说到，Zytiga延长了之前曾接受治疗并且几乎没有其他有用的治疗选择的晚期前列腺癌患者的生命。

一项纳入了1195例之前曾接受过多西他赛化疗的晚期去势抵抗前列腺癌患者的临床研究验证了Zytiga的安全性和有效性。这些患者随机接受Zytiga（每日一次）联合泼尼松（每日两次）或安慰剂（糖丸，每日两次）联合泼尼松治疗。

该项研究旨在测量晚期去势抵抗前列腺癌患者的整体存活率和从治疗开始到病人的死亡的时间。Zytiga联合泼尼松组患者的整体生存期为14.8个月，而安慰剂联合泼尼松组为10.9个月。

接受Zytiga治疗的患者报告的最常见的副作用包括关节肿胀或不适、血钾水平低、体液滞留（通常是腿和脚）、肌肉不适、潮热、腹泻、尿路感染、咳嗽、高血压、心跳异常、尿频、夜间排尿增加、肠胃不适或消化不良和上呼吸道感染

Horsham, Pa., April 28, 2011– Centocor Ortho Biotech Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved ZYTIGA™ (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.

Androgens are hormones that promote the development and maintenance of male sex characteristics. However, in prostate cancer, androgens can help fuel the tumor’s growth. Androgen production primarily occurs in the testes and adrenal glands; in men with prostate cancer, the tumor tissue is an additional source of androgens. ZYTIGA is an oral androgen biosynthesis inhibitor that works by inhibiting the CYP17 enzyme complex, which is required for the production of androgens at these three sources.

“This FDA approval represents a welcome new option in the treatment of metastatic prostate cancer,” said Howard Scher, MD, Chief of the Genitourinary Oncology Service, Sidney Kimmel Center for Urologic and Prostate Cancers at Memorial Sloan-Kettering, and one of the co-lead investigators for the Phase 3 clinical study. “As a clinician, I believe the efficacy and safety profile of abiraterone acetate, as well as its oral, once-daily formulation, will help address the important need for additional therapeutic choices for men living with this serious disease.”

“In a Phase 3 study, treatment with ZYTIGA plus prednisone showed a significant increase in median survival compared with placebo plus prednisone,” said Professor Johann S. de Bono, MD, FRCP, MSc, PhD, The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, and one of the co-lead investigators for the Phase 3 clinical study. “It’s an exciting time for men with prostate cancer, and I believe that ZYTIGA will play an essential role in clinical practice.”

Results of the pivotal Phase 3, randomized, placebo-controlled, multicenter study showed that at pre-specified interim analysis, treatment with ZYTIGA in combination with prednisone resulted in a 35 percent reduction in the risk of death (14.8 months vs. 10.9 months [hazard ratio (HR) = 0.646; 95 percent CI: 0.543, 0.768; p<0.0001]) and a 3.9 month difference in median survival compared to placebo plus prednisone. In an updated analysis, results were consistent with those from the interim analysis with a 4.6 month difference between the two arms in median survival (15.8 months vs. 11.2 months [HR = 0.74]).

At a predetermined number of events in the study, an interim analysis was conducted and it was determined that efficacy had been demonstrated. At that time, the study was unblinded at the recommendation of the Independent Data Monitoring Committee. Information regarding these results can be found at: http://www.centocororthobiotech.com/cobi/viewDocumentByTitleAlias.html?title=PR_101110.

The most common adverse reactions (greater than or equal to 5 percent) reported in the clinical study were: joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia and upper respiratory tract infection. Additional information is included in the Important Safety Information below.

“Prostate cancer is a significant public health threat in the United States,” said Wendy L. Poage, MHA, President, Prostate Conditions Education Council, a national organization committed to men’s health. “ZYTIGA is an important new option and a welcome addition to the armamentarium we have to fight this deadly disease.”

Pivotal Study Design

ZYTIGA, in combination with prednisone, was evaluated in a Phase 3, randomized, placebo-controlled, multicenter clinical study in patients who had received prior chemotherapy containing a taxane (N = 1,195). Patients were randomized 2:1 to receive ZYTIGA 1 gram daily in combination with prednisone 5 milligrams (mg) twice daily or placebo in combination with prednisone 5 mg twice daily (control arm).