１２月２９日电  美国食品和药物管理局２９日宣布，一种治疗晚期前列腺癌的新药Ｄｅｇａｒｅｌｉｘ获准在美国上市，这是美药管局７年来首次批准治疗前列腺癌的新药上市。这种新型注射药剂主要针对晚期前列腺癌患者，它属于“促性腺激素释放激素（ＧｎＲＨ）”受体抑制剂类药物，通过抑制睾丸激素来延缓前列腺癌病程发展。美药管局负责肿瘤学药物产品的官员理查德•帕兹杜尔当天在新闻公报中说，前列腺癌是美国男性的第二大“癌症杀手”，“这些患者需要更多的治疗选择”。 据美国媒体报道，此前一些激素疗法的特点是“先升后降”，即在治疗初期，某些疗法会导致患者的睾丸激素水平激增，然后才会显现疗效，降低睾丸激素水平。这意味着在治疗初期，肿瘤可能非但未被抑制，反而会刺激生长。而Ｄｅｇａｒｅｌｉｘ从一开始就能抑制前列腺癌。前列腺癌是男性中最常见的癌症类型之一。据美媒体报道，在２００４年，美国有近１９万名男性被诊断患上前列腺癌，另有２．９万名患者死于这种疾病。目前治疗前列腺癌的疗法除激素疗法外，还有前列腺切除术、放疗和化疗等。
On December 24, 2008, the U. S. Food and Drug Administration (FDA) approved degarelix for injection (Ferring Pharmaceuticals Inc., Parsippany, NJ), a new gonadotropin releasing hormone (GnRH) receptor antagonist, for the treatment of patients with advanced prostate cancer.  This indication is based on degarelix’s effectiveness in attaining and maintaining serum testosterone suppression to medical castration levels during 12 months of treatment in an open-label, randomized, multi-center, parallel-group study.
A total of 620 patients were randomized to receive one of two degarelix dosing regimens or leuprolide for one year:  degarelix at a starting dose of 240 mg followed by monthly doses of 160 mg subcutaneously, degarelix at a starting dose of 240 mg followed by monthly doses of 80 mg subcutaneously, or monthly doses of leuprolide 7.5 mg intramuscularly.  The primary objective was to demonstrate that degarelix is effective in achieving and maintaining testosterone suppression to castration levels ( ≤ 50 ng/dL) during 12 months of treatment.  The medical castration rates were 98.3% (95% CI: 94.8%; 99.4%) in the degarelix 240/160 mg arm, 97.2% (95% CI: 93.5%; 98.8%) in degarelix 240/80 mg arm, and 96.4% (95% CI: 92.5%; 98.2%) in the leuprolide 7.5 mg arm. The key secondary analyses showed that no testosterone surges were observed in the degarelix arms and that 96% of patients attained medical castration 3 days after the first degarelix dose compared to no patients receiving leuprolide.
The most commonly observed adverse reactions (frequency of <10%) in either degarelix arm included injection site reactions (e.g., pain, erythema, swelling or induration), hot flashes, weight increase, and increases in transaminases and gamma-glutamyltransferase. The majority of the adverse reactions were grade 1/2 in severity; grade 3/4 adverse reactions were uncommon. The injection site reactions were transient, with frequencies of 35-44% in the degarelix arms compared to a frequency of <1% in the leuprolide arm. Hepatic laboratory abnormalities were generally reversible, with grade 3 abnormalities in less than 1% of patients. There were no important differences in adverse reactions between the two degarelix arms, except for fewer injection site reactions in the 240/80 mg arm.
 
The recommended dosing regimen is a starting dose of 240 mg given as two subcutaneous injections of 120 mg each followed by monthly maintenance doses of 80 mg given as a single subcutaneous injection.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at
FDA Approves Degarelix
The U.S. Food and Drug Administration (FDA) has approved degarelix, an injectable gonadotropin-releasing hormone (GnRH) receptor antagonist, indicated for patients with advanced prostate cancer. Potential trade names are still under review with the FDA.
Phase III studies showed that degarelix is at least as effective as leuprolide (Lupron Depot(R)) in sustaining castrate levels or lower of testosterone, and had a statistically significant faster reduction of testosterone. At Day 3 of treatment, 96% of degarelix patients achieved castrate levels of testosterone, compared with zero percent receiving leuprolide. By Day 14, 99% of degarelix patients achieved castrate levels of testosterone, compared with 18% receiving leuprolide.
In the clinical trial, prostate specific antigen (PSA) levels were also monitored as a secondary endpoint. PSA levels were lowered by 64% two weeks after administration of degarelix, 85% after one month, 95% after three months, and remained suppressed throughout the one year of treatment. These PSA results should be interpreted with caution because of the heterogeneity of the patient population studied. No evidence has shown that the rapidity of PSA decline is related to a clinical benefit.
Prostate cancer is known to grow in the presence of testosterone. Suppression of testosterone has been a treatment goal for advanced prostate cancer for many years. Surgical castration was the standard method of reducing testosterone from the 1940s until the mid-1980s when the earliest forms of medical castration, luteinizing hormone releasing hormone (LHRH) agonists, were introduced.
Degarelix is the only GnRH receptor antagonist approved by the FDA for the treatment of hormonally-sensitive advanced prostate cancer. Degarelix achieves medical castration differently than LHRH agonists, specifically by binding reversibly to GnRH receptors on cells in the pituitary gland, quickly reducing the release of gonadotropins and consequently testosterone.
Overall, the most commonly observed adverse reactions during degarelix therapy included injection site reactions (e.g. pain, erythema, swelling or induration), hot flushes, increased weight, fatigue, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT). 99% of these observed adverse reactions were Grade 1 or 2 (mild to moderate). Specifically relating to the injection site adverse reactions, most were transient, of mild to moderate intensity, occurred primarily with the starting dose and led to few discontinuations (<1%). Grade 3 (severe) injection site reactions occurred in 2% or less of patients receiving degarelix. Degarelix is contraindicated in patients with known hypersensitivity to degarelix or to any of the product components. Degarelix is not indicated in women or pediatric patients. Long-term androgen deprivation therapy prolongs the QT interval. Physicians should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, electrolyte abnormalities, or congestive heart failure and in patients taking Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medications.
Degarelix Paitent Information
Read this patient information leaflet before you start taking degarelix and each time you get a refill.
There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
What is degarelix?
Degarelix is a prescrpition medicine used in the treatment of advanced prostate cancer.
It is not known if degarelix is safe or effective in children.
Who should not use degarelix?
Degarelix should not be given to:
• people who are allergic to any of the other ingredients in degarelix. See the end of this leaflet for a complete list of ingredients in degarelix
• women who are pregnant or may become pregnant
Talk to your healthcare provider before getting degarelix if you have any of these conditions.
What should I tell my healthcare provider before receiving degarelix?
Before receiving degarelix, tell your healthcare provider about all your medical conditions, including if you:
• have any heart problems
• have problems with balance of your body salts or electrolytes, such as sodium, potassium, calcium,and magnesium
• have kidney or liver problems
• are breast-feeding or plan to breast-feed. It is not known if degarelix passes into your breast milk. You and your healthcare provider should decide if you will take degarelix or breast feed. You should not do both without talking with your healthcare provider.
Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you are taking or have taken any medicines for your heart.
Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.
How should I receive degarelix?
• You will receive an injection of degarelix from your healthcare provider.
• The injection site will always be in the abdominal area but will change within that area with the next doses of degarelix.
• The injected medicine gives you a continuous release of degarelix over one month.
• Two injections are given as a first dose and the following monthly doses are one injection.
• Make sure your injection site is free of any pressure from belts, waistbands or other types of clothing.
• Always set up an appointment for your next injection.
• If you miss a dose of degarelix, or if you think you forgot to get your monthly dose of degarelix, talk to your healthcare provider about how to get your next dose.
What are the possible side effects of degarelix?
The common side effects include:
• hot flashes
• injection site pain, redness, and swelling, especially with the first dose
• weight gain
• increase in some liver enzymes
• tiredness
• hypertension
• back and joint pain
• chills
• urinary tract infection
• decreased sex drive and trouble with erectile function (impotence)
These are not all the possible side effects. For more information, ask your healthcare provider or pharmacist.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of degarelix.
Medicines are sometimes prescribed for conditions that are not mentioned in the patient leaflet. Do not use degarelix for a condition for which it was not prescribed. Do not give degarelix to other people, even if they have the same symptoms that you have. It may harm them.
This patient information leaflet summarizes the most important information about degarelix. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about degarelix that is written for health professionals.
For more information, call 1-888-FERRING (1-888-337-7464)
What are the ingredients in degarelix?
Active ingredient: degarelix (as acetate)
Inactive ingredient: mannitol
FDA核准： Fludarabine Phosphate 与 Degarelix