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导读：FDA批准其治疗脑癌的专利药：以聚苯丙生20为载体的卡莫司汀植入膜剂为罕用药，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
Guilford制药公司日前宣布，FDA批准其治疗脑癌的专利药：以聚苯丙生20为载体的卡莫司汀植入膜剂（polifeprosan 20 with carmustine implant，Gliadel）为罕用药，在治疗接受一期切除术的恶性胶质瘤患者领域享有7年的市场独占期。按照罕用药法案（Orphan Drug Act）规定，该独占期始于获得批准的日期即2003年2月，终止于2010年2月。
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。
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 with aggressive and prolonged corticosteroid treatment
Begin anticonvulsants 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 not replace the services of a physician or doctor-patient relationship. 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.
Surgicel is a registered trademark of Johnson & Johnson.
References
Prescribing 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.
Please see the Prescribing Information for more information.
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