Gliadel为一种白色至灰白色的一角硬币大小的薄膜，包含生物可降解聚合物聚苯丙生20和7.7mg卡莫司汀（carmustine，BCNU），卡莫司汀是治疗恶性胶质瘤的常用静脉给药的化疗药物。 关键字：卡莫司汀植入膜剂(Gliadel) Gliadel为一种白色至灰白色的一角硬币大小的薄膜，包含生物可降解聚合物聚苯丙生20和7.7mg卡莫司汀（carmustine，BCNU），卡莫司汀是治疗恶性胶质瘤的常用静脉给药的化疗药物。当手术切除脑瘤时，在经手术创建的空腔中可最多植入8片本品。在植入处，Gliadel将缓慢溶解，直接向肿瘤部位释放高浓度卡莫司汀，使扩撒到其它部位的药物减至最少。  Gliadel适应证是新诊断为高度恶性胶质瘤的患者的手术和放疗辅助药物，也可作为多形性胶质母细胞瘤（GBM）复发患者的手术辅助用药。  卡莫司汀植入膜剂(Gliadel)——全球第一个治疗脑癌的专利药品 Polifeprosan 20 with Carmustine Implant Gliadel Wafer格立得植入剂   成分及性状 Gliadel Wafer为直径1.45公分、厚约1公厘的灰白至淡黄色无菌植入製剂。每一片含可生物分解的聚酸酐polifeprosan 20 (polyanhydridecopolymer) 192.3 毫克及carmustine 7.7 毫克。Carmustine均匀分布於polifeprosan 20基质中，并由prolifeprosan 20负责控制carmustine的局部传送。   作用 Gliadel Wafer能够直接将carmustine释放至脑癌摘除手术后所造成的腔室内，并扩散至週边的脑组织，藉由对DNA及RNA的烷基化作用而发挥抗惡性肿瘤作用。   药物动力学 Gliadel Wafer中的polifeprosan 20，在动物实验中发现，超过70%於三週内分解，分解后的单体包括carboxyphenoxypropane经由肾臟排除，而sebacic acid则经由肝臟代谢成二氧化碳排出体外。Prolifeprosan 20 在人体内的吸收、分佈、代谢及排除等特性尚不清楚。Gliadel Wafer释放至人体脑腔的carmustine浓度也尚无测量值。植入脑癌摘除手术后腔室的Gliadel Wafer能被生物分解，分解率因人而異。即使所有成分皆被充分分解，但於分解过程中，脑部影像扫瞄或再次手术皆可見到植入剂残餘物尚留在脑内。   适应症 作为復发性多形性神经胶母细胞瘤病人的手术辅助。   不良反应 1. 癲癇发作：高度惡性神经胶质瘤復发病人之再次手术臨床试验发现，兩组病人的癲癇发作率为19%，手术后五天内癲癇发作的发生率为54% (12/22，Gliadel Wafer组)及9% (2/22，安慰剂组)。手术后第一次癲癇发作时间的平均天數为Gliadel Wafer组3.5天，安慰剂组61天。 2. 脑水肿：新诊断罹患高度惡性神经胶质瘤病人之手术治療臨床试验显示，脑水肿发生率为22.5% (Gliadel Wafer组)及19.2%(安慰剂组)。脑水肿伴随肿块时(可能原因有肿瘤復发、颅内感染、坏死)，可能需要再次手术，有些病人甚至必须取出Gliadel Wafer或其残留物。 3. 伤口癒合異常：高度惡性神经胶质瘤復发病人之再次手术臨床试验，伤口癒合異常发生率为14%(Gliadel Wafer组)及5%(安慰剂组)。 4. 颅内感染：高度惡性神经胶质瘤復发病人之再次手术臨床试验中，脑脓疡或脑膜炎的发生率为4%(Gliadel Wafer 组) 及1%( 安慰剂组)。   注意事项 手术摘除后的腔室应避免与脑室相通，以预防Gliadel Wafer移位至脑室，造成阻塞性水脑。如肿瘤摘除后之腔室与脑室之缺口大於GliadelWafer 的直径， 应填补缺口后再植入GliadelWafer。   禁忌 已知对carmustine或本药品其它任一成分过敏的病人禁忌投与Gliadel Wafer。   交互作用 目前尚无Gliadel Wafer与其它药品交互作用的研究。化学治療併Gliadel Wafer的短期及长期毒性试验结果尚未完成。放射性治療併GliadelWafer未見任何短期或慢性毒性。   剂量及用法 每一片Gliadel Wafer含carmustine 7.7 mg，手术植入八片等於投与剂量61.6 mg。一般建议剂量：於脑癌摘除手术后所造成的腔室内植入Gliadel Wafer八片。若空间不够植入八片，则尽可能以最大能植入的片數植入。目前尚无单次手术植入Gliadel Wafer八片以上的臨床经验，因此不建议植入八片以上。 Gliadel Wafer对儿童的安全性及有效性尚未建立。    储存 零下20°C以下。 --------------------------------------------------------------- 原产地英文商品名: GLIADEL WAFER 原产地英文药品名: Polifeprosan 20 with Carmustine Implant 原产地英文化合物名称: Carmustine 中文参考商品译名: 格立得植入剂 中文参考药品译名: 卡莫司汀植入膜剂 中文参考化合物名称: 可生物分解的聚酸酐192.3毫克及卡莫司汀7.7毫克 曾用名: 卡氮芥、氯乙亚硝脲、亚硝基脲 生产厂家中文参考译名: Eisai公司 生产厂家英文名: Eisai Corporation --------------------------------------------------------------- 该药品相关信息网址1: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails 卡莫司汀植入膜剂(格立得植入剂Gliadel)—是全球唯一治疗恶性胶质瘤的希望药物 GLIADEL WAFER格立得植入剂（卡莫司汀植入膜剂） How to Use GLIADEL® Wafer Six Steps to Using GLIADEL® Wafer 1. Preparation for Use Maximize resection of tumor Send tumor specimen to pathologist to confirm malignant glioma Achieve hemostasis before implantation to eliminate bleeding Obtain clear irrigation fluid 2. Handle Wafers carefully due to fragility and toxicity of carmustine Use double surgical gloves Use a surgical instrument dedicated to wafer handling Keep wafer pouches unopened until implantation 3. Opening the GLIADEL pouch (outer surface of foil pouch is not sterile) Open outer pouch: peel folded corner in outward motion Do not pull downward this may break wafer Remove inner pouch: with forceps, grab crimped edge, pull upwards Open inner pouch: gently hold crimped edge, cut around wafer Remove wafer: gently grasp with forceps, place onto sterile field 4. Implanting GLIADEL Line resection cavity surface with wafers Cover entire surface of cavity using mosaic pattern, using up to eight wafers (7.7 mg carmustine each) Pack wafers close without stacking; slight overlap and halving wafers are acceptable If necessary,stretch surface area to maximize exposure to wafers Prevent wafer migration into ventricular system and obstructive hydrocephalus by closing any communication larger than a wafer before implantation Dispose of unused wafers 5. Securing the Wafers Anchor wafers with ½-inch-wide strips of Surgicel® (oxidized cellulose), starting at bottom of cavity and moving up Keep Surgicel® strips 1 layer deep: do not create large mass 6. Ensure watertight dural closure Take extra care to decrease risk of CSF leaks and infection Suction to ensure no blood in cavity Irrigate resection cavity before closure If necessary, use a graft of autologous, nonsynthetic or synthetic dura patch or substitute Treat CSF leaks aggressively Manage edema withaggressiveandprolongedcorticosteroidtreatmentBeginanticonvulsants before surgery (recommended for all patients) The information described above is a general example intended to help educate individuals on GLIADEL® Wafer. The information provided is neither a substitute for professional medical advice nor intended to provide treatment options. The text and graphics depicted do notreplacetheservicesofaphysicianordoctorpatientrelationship. The use of the information is at the discretion of the reader. The reader should always consult a qualified medical expert in the use of GLIADEL® Wafer. Eisai makes no representations or warranties with respect to any information provided on this graphic and is not liable for any direct or indirect claim, loss or damage resulting from the use of this information. Important Safety Information Indications: GLIADEL® Wafer is indicated in patients with newly diagnosed high-grade malignant glioma as an adjunct to surgery and radiation. GLIADEL is also indicated in patients with recurrent glioblastoma multiforme as an adjunct to surgery. Contraindication: GLIADEL® Wafer should not be given to patients who have demonstrated a previous hypersensitivity to carmustine or any of the components of GLIADEL. Warnings: Patients undergoing craniotomy for malignant glioma and implantation of GLIADEL should be monitored closely for known complications of craniotomy, including seizures, intracranial infections, abnormal wound healing, and brain edema. Cases of intracerebral mass effect unresponsive to corticosteroids have been described in patients treated with GLIADEL, including one case leading to brain herniation. Precautions: Communication between the surgical resection cavity and the ventricular system should be avoided to prevent the wafers from migrating into the ventricular system and causing obstructive hydrocephalus. If a communication larger than the diameter of a wafer exists, it should be closed prior to wafer implantation. Computed tomography and magnetic resonance imaging of the head may demonstrate enhancement in the brain tissue surrounding the resection cavity after implantation of GLIADEL. This enhancement may represent edema and inflammation caused by GLIADEL or tumor progression. The short-term and long-term toxicity profiles of GLIADEL when given in conjunction with chemotherapy have not been fully explored. Pregnancy and Nursing: There are no studies assessing the reproductive toxicity of GLIADEL. Carmustine, the active component of GLIADEL, can cause fetal harm when administered to a pregnant woman. It is recommended that patients receiving GLIADEL discontinue nursing. Adverse Events: Seizures: In the initial surgery trial, the incidence of seizures was 33.3% in patients receiving GLIADEL and 37.5% in patients receiving placebo. Grand mal seizures occurred in 5% of GLIADEL-treated patients and 4.2% of placebo-treated patients. The incidence of seizures within the first 5 days after wafer implantation was 2.5% in the GLIADEL group and 4.2% in the placebo group. In the surgery for recurrent disease trial, the incidence of post-operative seizures was 19% in both patients receiving GLIADEL and placebo. In this study, 12/22 (54%) of patients treated with GLIADEL and 2/22 (9%) of placebo patients experienced the first new or worsened seizure within the first five post-operative days. The median time to onset of the first new or worsened post-operative seizure was 3.5 days in patients treated with GLIADEL and 61 days in placebo patients. Brain Edema: In the initial surgery trial, brain edema was noted in 22.5% of patients treated with GLIADEL and in 19.2% of patients treated with placebo. Development of brain edema with mass effect (due to tumor recurrences, intracranial infection, or necrosis) may necessitate re-operation and, in some cases, removal of GLIADEL or its remnants. Healing Abnormalities: The following healing abnormalities have been reported in clinical trials of GLIADEL: wound dehiscence, delayed wound healing, subdural, subgaleal or wound effusions, and cerebrospinal fluid leak. In the initial surgery trial, healing abnormalities occurred in 15.8% of GLIADEL-treated patients and in 11.7% of placebo recipients. Cerebrospinal fluid leaks occurred in 5% of GLIADEL recipients and 0.8% of those given placebo. During surgery, a water-tight dural closure should be obtained to minimize the risk of cerebrospinal fluid leak. In the surgery for recurrent disease trial, the incidence of healing abnormalities was the 14% of GLIADEL treated patients and 5% in patients receiving placebo wafers. Intracranial Infection: In the initial surgery trial, the incidence of brain abscess or meningitis was 5% in patients treated with GLIADEL and 6% in patients receiving placebo. In the recurrent setting, the incidence of brain abscess or meningitis was 4% in patients treated with GLIADEL and 1% in patients receiving placebo. FDA已批准Gilladel Wafer 辅助治疗恶性神经胶质瘤 FDA已批准GilladelWafer用于辅助手术和放疗治疗高度恶性神经胶质瘤。　　 Gliadelwafer是目前上市的唯一一种可将化疗药物直接传输到脑部癌症病灶处的癌症疗法，它可绕过血脑屏障，使脑部其他部位尽可能少地受到药物影响。　　 Gliadelwafer由含有7.7mg卡氯芥的生物降解聚合材料构成。当手术将脑瘤清除后，可在病灶空穴内植入最多达8个的Gliadelwafer。这些Gliadelwafer可以慢慢溶解，直接向肿瘤处释放高浓度的BCNU，同时将药物对身体其他部位的影响降至最小。　　 在14个国家38个医学中心进行的III期双盲，安慰剂对照的临床试验中，240名接受了初次手术切除高度恶性神经瘤的男女患者随机在切除空穴中植入Gliadelwafer或安慰剂，接着两周后进行放疗。　　 240名病人中的239名接受了48个月的跟踪访问。在最后一次的随访中，有11名病人仍健在，其中9人是Gliadelwafer治疗组，2人为安慰剂组。Gliadelwafer组的平均存活期从11.6个月延长至13.9个月。在治疗后三年四年中，整个死亡危险减少了，这从危险机率为0.73这一数值中可得以反映。 How GLIADEL® Wafer is Used GLIADEL Wafer is implanted in the brain along the walls and floor of the cavity created after a malignant glioma has been surgically removed. Up to 8 wafers may be placed in the area where the tumor was located. The number of wafers implanted depends on the size of the space left after the removal of the tumor. As they dissolve, the wafers release carmustine into the surrounding cells. GLIADEL Wafer is implanted in the brain along the walls and floor of the cavity created after a malignant glioma has been surgically removed. A surgeon may place up to 8 wafers. The graphic above shows a cavity in which 6 wafers were implanted. Important Questions About GLIADEL Wafer Indications GLIADEL® Wafer (polifeprosan 20 with carmustine implant) is indicated in patients with newly diagnosed high-grade malignant glioma as an adjunct to surgery and radiation. GLIADEL Wafer is also indicated in patients with recurrent glioblastoma multiforme as an adjunct to surgery. Important Safety Information You should not be given GLIADEL Wafer if you are allergic to carmustine or any of the components of GLIADEL Wafer. If you are undergoing surgery for malignant glioma and implantation of GLIADEL Wafer, you should be monitored closely for known complications, including convulsions, infections, abnormal wound healing, and swelling of the brain. If you are pregnant or are planning to become pregnant, you should understand that carmustine, the active component of GLIADEL Wafer, can cause harm to the fetus if given to a pregnant woman. It is not known if either carmustine, or other components of GLIADEL Wafer are excreted in human milk. Many drugs are excreted in human milk and there is a risk for serious side effects from carmustine in nursing infants; therefore discontinuation of nursing is recommended if you will be receiving GLIADEL Wafer. It is possible that if GLIADEL Wafers are not implanted properly, they could block the flow of cerebrospinal fluid and might cause abnormal accumulation of fluid in the brain (obstructive hydrocephalus). The short-term and long-term safety of GLIADEL Wafer when given together with chemotherapy is not fully known. Following surgery to remove a brain tumor and implantation of GLIADEL Wafer, the following side effects have been reported in clinical studies: Seizures (convulsions): In clinical studies, seizures have occurred within days or several weeks following implantation of GLIADEL Wafer. Both new seizures and worsening of seizures have been reported. Brain Swelling: Brain swelling has occurred in clinical studies. In some cases, brain swelling may require another surgery, and removal of GLIADEL Wafers or remnants of the wafers may be required. Abnormal wound healing: In clinical studies, abnormal healing of the surgical wound has occurred following implantation of GLIADEL Wafer. These abnormalities included reopening of the surgical area, leaking of brain or spinal fluid, delays in healing, or other abnormalities in how the wound heals. Brain Infections: In clinical studies, brain infections, including meningitis, have occurred following implantation of GLIADEL Wafer. Please read the full Prescribing Information and discuss it with your doctor or healthcare professional. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.