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2010年4月29日美国食品药品监督管理局（FDA）今日批准Provenge (sipuleucel-T)一种新的用于治疗某些晚期前列腺癌患者的药物，该药可通过激发患者自身免疫系统来抵抗这种疾病。Provenge适用于治疗已扩散至人体其他部位并且常规激素治疗无效的无症状或症状轻微的前列腺癌。
在美国，前列腺癌是男性中仅次于皮肤癌的第二常见癌症类型，通常发生于老年男性。根据美国国家癌症研究所（National Cancer Institute）的统计，2009年约有192000个新的前列腺癌病例被诊断出，并且约有27000人死于该病。FDA生物制品评估和研究中心的执行主任Karen Midthun博士表示，“Provenge的获批为目前治疗药物有限的晚期前列腺癌患者提供了一种新的选择。”
Provenge是一种自体源性细胞免疫疗法药（autologous cellular immunotherapy），可激发患者自身免疫系统对前列腺癌作出反应。每剂Provenge均通过一种用于白细胞去除术（leukapheresis）的机器提取患者血液中的免疫细胞而制备的。为增强这些免疫细胞对前列腺癌的反应，这些细胞随后会被暴露于一种在多数前列腺癌中存在的蛋白质，并结合为一种免疫激发物质（immune stimulating substance）。在这个过程之后，患者的自身免疫细胞会返回至其体内以治疗这种前列腺癌。Provenge大约每隔2周静脉注射3剂。
在一项纳入512名激素治疗无效的转移性前列腺癌患者的随机、双盲、安慰剂对照、多中心试验中，对Provenge的有效性进行了研究，该研究显示（接受Provenge治疗的患者较未接受该药治疗者）其总体生存期增加4.1个月。接受Provenge治疗的患者的中位生存期为25.8个月，而与之相对照的未接受该药治疗患者的中位生存期则为21.7个月。
几乎所有接受Provenge治疗的患者都曾发生过某种类型的不良反应。已报告的常见不良反应包括寒战、疲劳、发热、背痛、恶心、关节痛和头痛。大部分不良反应为轻度或中度。在大约1/4接受Provenge治疗的患者中已报告的严重不良反应包括一些急性输注反应和中风。在Provenge组中3.5%的患者被观察到有心血管事件发生，包括出血性和局部缺血性中风，而对照组为2.6%。Provenge由位于Seattle的Dendreon公司生产。
PROVENGE(sipuleucel T)说明书
Manufacturer:
Dendreon Corporation
Pharmacological Class:
Autologous cellular immunotherapy.
Active Ingredient(s):
Sipuleucel-T (autologous CD54+ cells activated with PAP-GM-CSF); minimum 50 million cells/dose; suspension for IV infusion.
Indication(s):
Asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.
Pharmacology:
Sipuleucel-T is an autologous cellular immunotherapy designed to induce an immune response targeted against prostatic acid phosphatase (PAP), an antigen expressed in most prostate cancers. During ex vivo culture with PAP-GM-CSF, antigen-presenting cells (APCs) take up and process the recombinant target antigen into small peptides that are then displayed on the APC surface. The product consists of autologous peripheral blood mononuclear cells, including APCs, that have been activated during a defined culture period with a recombinant antigen consisting of PAP linked to an immune cell activator, granulocyte-macrophage colony-stimulating factor (GM-CSF). The patient’s peripheral blood mononuclear cells are obtained by standard leukapheresis about 3 days before the infusion date. Both patient and physician must adhere to the personalized leukapheresis and infusion schedules.
In addition to the minimal 50 million autologous CD54+ activated cells, the product also contains T cells, B cells, natural killer cells, and others, and may contain residual amounts of intact PAP-GM-CSF.
Clinical Trials:
The effect of sipuleucel-T on patients with metastatic hormone refractory prostate cancer was studied in three similar placebo-controlled trials. After randomization, patients underwent a series of 3 leukapheresis procedures followed by an infusion of either sipuleucel-T or control (unactivated autologous peripheral mononuclear cells). After treatment, patients were followed and treated according to the discretion of their physicians.
In Study 1, 512 patients were randomized in a 2:1 ratio to receive sipuleucel-T or control. This study excluded patients with visceral metastases and moderate-to-severe cancer-related pain, and all patients had baseline testosterone levels <50ng/mL. In Study 2, a similar study in 127 patients with no cancer-related pain, the primary endpoint was time to disease progression. Analysis of the primary endpoint did not reach statistical significance. A third study was terminated before completion of planned accrual.
For Study 1, the overall median survival for patients treated with sipuleucel-T was 25.8 months, compared to 21.7 months for control. For Study 2, the overall survival results were 25.9 months for the sipuleucel-T group and 21.4 months for the control group.
Legal Classification:
Rx
Adults:
Autologous use only. Obtain product release from manufacturer, match patient identity on product and Cell Product Disposition form, check expiration date and time on product before infusing. Premedicate 30 minutes before infusion with acetaminophen and antihistamine. Give three doses at 2-week intervals. For each dose: give entire contents of bag by IV infusion over 60 minutes; do not use filter; do not use if clumps do not disperse with gentle mixing. Observe patient for at least 30 minutes after infusion. May interrupt or slow infusion if acute transfusion reaction occurs; do not restart if product at room temp for >3 hours.
Children:
Not applicable.
Warnings/Precautions:
Cardiac or pulmonary conditions. Each dose requires a standard leukapheresis procedure about 3 days before infusion. If scheduled infusion is missed, do an additional leukapheresis procedure if treatment course is to be continued. Risk of disease transmission. Pregnancy, lactation: not applicable.
Interaction(s):
May be antagonized by concomitant chemotherapy or immunosuppressive therapy.
Adverse Reaction(s):
Infusion reactions (eg, chills, fever, respiratory events, GI upset, hypertension, tachycardia), fatigue, back pain, joint ache, headache.
Notes:
If product sterility tests indicate microbial contamination, manufacturer will contact physician (tests are incomplete at time of infusion).
How Supplied:
Patient-specific bag (250mL)—1
Last Updated:
10/28/2010
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm210174.htm
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