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.

适应证和用途
ZYTIGA是一种CYP17抑制剂适用于与泼尼松联用为治疗既往接受含多烯紫杉醇[docetaxel]化疗转移去势难治性前列腺癌患者。

剂量和给药方法
推荐剂量：ZYTIGA 1,000 mg口服给予每天1次与泼尼松联用5 mg口服给予每天2次。必须空腹服用ZYTIGA。在服用ZYTIGA 剂量前至少2小时和服用ZYTIGA剂量后至少1小时不应消耗食物。
（1）对基线中度肝受损(Child-Pugh类别B)患者，减低ZYTIGA开始剂量至250 mg每天1次。
（2）对治疗期间发生肝毒性患者，不用ZYTIGA直至恢复。可在减低剂量再次治疗。如患者发生严重肝毒性应终止ZYTIGA。

剂型和规格
250 mg片

禁忌证
妊娠或可能成为妊娠妇女禁忌用ZYTIGA。

警告和注意事项
（1）盐皮质激素过量：有心血管疾病史患者谨慎使用ZYTIGA。尚未确定在有射血分量LVEF < 50%或NYHA类别III或IV心衰患者中ZYTIGA的安全性。治疗前控制高血压和纠正低钾血症。至少每月1次监查血压，血清钾和液体潴留症状。
（2）肾上腺皮质功能不全：监视肾上腺皮质功能不全的症状和征象。应急情况前，期间和后可能适应增加皮质激素剂量。
（3）肝毒性：肝酶增加曾导致药物中断，剂量调整和/或终止。监查肝功能和如建议调整，中断或终止ZYTIGA给药。
（4）食物影响：必须空腹服用ZYTIGA。当与食物同时服用醋酸阿比特龙[abiraterone acetate]阿比特龙的暴露(曲线下面积)增加达10倍。

不良反应
最常见不良反应(≥ 5%)是关节肿胀或不适，低钾血症，水肿，肌肉不适，热潮红，腹泻，泌尿道感染，咳嗽，高血压，心律失常，尿频，夜尿，消化不良，和上呼吸道感染。

药物相互作用
ZYTIGA是一种肝药物代谢酶CYP2D6是抑制剂。因为治疗指数窄，避免ZYTIGA与CYP2D6底物共同给药。如果不能使用另外治疗，小心对待和考虑减低同时给予CYP2D6底物剂量。

特殊人群中使用
在基线严重肝受损(Child-Pugh类别 C)患者中不要使用ZYTIGA。

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).
Indication
ZYTIGA™ (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC) who have received prior chemotherapy containing docetaxel.

Important Safety Information

Contraindications

ZYTIGA™ may cause fetal harm (Pregnancy Category X) and is contraindicated in women who are or may become pregnant.
Warnings and Precautions

Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess
Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in hypertension, hypokalemia and fluid retention. Safety has not been established in patients with LVEF < 50% or NYHA Class III or IV heart failure. Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly.
Adrenocortical Insufficiency (AI) has been reported in clinical trials after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn or if the patient experiences unusual stress. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during and after stressful situations.
Hepatotoxicity - Increases in liver enzymes have led to drug interruption, dose modification and/or discontinuation. Monitor liver function and modify, withhold or discontinue ZYTIGA™ dosing as recommended (See Prescribing Information for more information).
Food Effect - ZYTIGA™ must be taken on an empty stomach. Exposure of abiraterone increases up to 10-fold when abiraterone acetate is taken with meals. No food should be eaten for at least two hours before the dose of ZYTIGA™ is taken and for at least one hour after the dose of ZYTIGA™ is taken.

Adverse Reactions

The most common adverse reactions (≥5%) reported in clinical trials 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.

Drug Interactions

ZYTIGA™ is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Avoid co-administration with CYP2D6 substrates that have a narrow therapeutic index. If an alternative cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate. Additionally, abiraterone is a substrate of CYP3A4 in vitro. Strong inhibitors and inducers of CYP3A4 should be avoided or used with caution.

About Metastatic Castration-Resistant Prostate Cancer
Metastatic castration-resistant prostate cancer or CRPC occurs when cancer has metastasized beyond the prostate and disease progresses despite serum testosterone below castrate levels.

The prostate is a gland located around the urethra (under the bladder) in men that produces part of the seminal fluid. In some cases, cancer of the prostate can grow slowly compared with other cancers. However, depending on factors including characteristics specific to the patient and the tumor, prostate cancer also can grow very quickly and spread widely.

Excluding skin cancer, prostate cancer is the most frequently diagnosed cancer in men in the United States. In 2010, more than 217,000 new cases of prostate cancer were estimated and more than 32,000 men died from the disease.

About ZYTIGA (abiraterone acetate)

ZYTIGA (abiraterone acetate) was developed by Ortho Biotech Oncology Research & Development, a Unit of Cougar Biotechnology, Inc., and will be marketed by Centocor Ortho Biotech Inc. Marketing applications for ZYTIGA have been filed with other regulatory authorities throughout the world.

ZYTIGA is the first oral, once-daily medication indicated for use in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel. For more information about ZYTIGA, visit www.ZYTIGA.com.

About Centocor Ortho Biotech Inc.

Centocor Ortho Biotech Inc. redefines the standard of care in immunology, nephrology and oncology. Built upon a pioneering history, Centocor Ortho Biotech Inc. harnesses innovations in large-molecule and small-molecule research to create important new therapeutic options. Beyond its innovative medicines, Centocor Ortho Biotech is at the forefront of developing education and public policy initiatives to ensure patients and their families, caregivers, advocates and health care professionals have access to the latest treatment information, support services and quality care. In addition to metastatic castration-restistant prostate cancer, Centocor Ortho Biotech markets oncology treatments for diseases such as recurrent ovarian cancer, relapsed or refractory multiple myeloma, hairy cell leukemia and anemia due to the effect of concomitantly administered chemotherapy. For more information about Centocor Ortho Biotech, visit www.centocororthobiotech.com.

Centocor Ortho Biotech Inc. is a member of the Johnson & Johnson Family of Companies.

About the Ortho Biotech Oncology Research & Development, unit of Cougar Biotechnology, Inc.

Ortho Biotech Oncology Research & Development, Unit of Cougar Biotechnology, Inc., partners with affiliated units and companies in the Janssen Pharmaceutical Companies, such as Centocor Ortho Biotech Inc. and Johnson & Johnson Pharmaceutical Research & Development, L.L.C., in the research and development of oncology and supportive care treatments.

* NOTE: Centocor Ortho Biotech Inc. provides support to Prostate Conditions Education Council for initiatives benefitting prostate cancer patients.