FDA批准GLIADEL薄片的应用扩展
Guilford公司于2月26日宣布，它已在销售的产品GLIADEL Wafer［聚苯丙生 20(polifeprosan 20)和卡莫司汀(carmustine)植入物］获FDA批准，用于新诊断 的高分化恶性神经胶质瘤病人,作为手术和放疗的辅助治疗。GLIADEL薄片是唯一 在销售的能将化疗药直接输送到脑癌部位的癌治疗药，从而绕过血脑屏障并最小 化地使药物与人体其他区域接触。它是一种白或米色一角硬币大小的薄片，由混 入7.7mg通常经静注给予的恶性神经胶质瘤治疗药卡莫司汀(BCNU)的生物可降解聚 合物组成。在手术切除脑肿瘤后留下的空腔内可植入多达8片GLIADEL薄片。在空 腔内薄片缓慢溶解，并高浓度地将BCNU直接释放到肿瘤部位。 在一项于14个国家38个癌治疗中心进行的双盲、安慰剂对照的Ⅲ期临床研究 中,共240例行第一次手术切除高分化恶性神经胶质瘤成年男性和女性患者于放疗 后2周随机接受植入GLIADEL薄片或安慰剂薄片。主要评价终点是存活状况。对239 例病人追访了48个月。在最后一次追访时还存活的11例病人中,9例接受过GLIADEL 和2例接受过安慰剂。GLIADEL治疗组病人的中数存活时间从11.6个月延长至13.9 个月(P＜0.05＝。治疗后3～4年间的总体死亡风险降低，其危险比为0.73(95% CI: 0.56-0.95,P＜0.05＝。

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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

GLIADEL^® Wafer (polifeprosan 20 with carmustine implant) should not be given to patients who have demonstrated a previous hypersensitivity to carmustine or any of the components of GLIADEL Wafer.

Patients undergoing craniotomy for malignant glioma and implantation of GLIADEL Wafer 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 Wafer, including 1 case leading to brain herniation.

Carmustine, the active component of GLIADEL Wafer, can cause fetal harm when administered to a pregnant woman. It is recommended that patients receiving GLIADEL Wafer discontinue nursing.

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.

CT and MRI of the head may demonstrate enhancement in the brain tissue surrounding the resection cavity after implantation of GLIADEL Wafer. This enhancement may represent edema and inflammation caused by GLIADEL Wafer or tumor progression.

The short-term and long-term toxicity profiles of GLIADEL Wafer when given in conjunction with chemotherapy have not been fully explored.

The following 4 categories of adverse events are possibly related to treatment with GLIADEL Wafer:

• Seizures: In the initial surgery trial, the incidence of seizures was 33.3% in patients receiving GLIADEL Wafer and 37.5% in patients receiving placebo. Grand mal seizures occurred in 5% of GLIADEL Wafer–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 Wafer 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 Wafer and placebo. In this study, 12/22 (54%) of patients treated with GLIADEL Wafer and 2/22 (9%) of placebo patients experienced the first new or worsened seizure within the first 5 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 Wafer 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 Wafer 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 Wafer or its remnants.
• Healing Abnormalities: The following healing abnormalities have been reported in GLIADEL Wafer clinical trials: 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 Wafer–treated patients and in 11.7% of placebo recipients. Cerebrospinal fluid leaks occurred in 5% of GLIADEL Wafer 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 14% in GLIADEL Wafer–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 Wafer and 6% in patients receiving placebo. In the recurrent setting, the incidence of brain abscess or meningitis was 4% in GLIADEL Wafer patients and 1% in patients receiving placebo.

Gliadel Dosage

This dosage information does not include all the information needed to use Gliadel safely and effectively. See full prescribing information for Gliadel. The information at Drugs.com is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.

Dosage and Administration for Gliadel

Each GLIADEL® Wafer contains 7.7 mg of carmustine, resulting in a dose of 61.6 mg when eight wafers are implanted. It is recommended that eight wafers be placed in the resection cavity if the size and shape of it allows. Should the size and shape not accommodate eight wafers, the maximum number of wafers as allowed should be placed. Since there is no clinical experience, no more than eight wafers should be used per surgical procedure.

Handling and Disposal1-7: Wafers should only be handled by personnel wearing surgical gloves because exposure to carmustine can cause severe burning and hyperpigmentation of the skin. Use of double gloves is recommended and the outer gloves should be discarded into a biohazard waste container after use. A surgical instrument dedicated to the handling of the wafers should be used for wafer implantation. If repeat neurosurgical intervention is indicated, any wafer or wafer remnant should be handled as a potentially cytotoxic agent.

GLIADEL® Wafer should be handled with care. The aluminum foil laminate pouches containing GLIADEL® Wafer should be delivered to the operating room and remain unopened until ready to implant the wafers. The outside surface of the outer foil pouch is not sterile.

Instructions for Opening Pouch Containing GLIADEL® Wafer

Figure 1: To remove the sterile inner pouch from the outer pouch, locate the folded corner and slowly pull in an outward motion.

Figure 2: Do NOT pull in a downward motion rolling knuckles over the pouch. This may exert pressure on the wafer and cause it to break.

Figure 3: Remove the inner pouch by grabbing hold of the crimped edge and pulling upward.

Figure 4: To open the inner pouch, gently hold the crimped edge and cut in an arc-like fashion around the wafer.

Figure 5: To remove the GLIADEL® Wafer, gently grasp the wafer with the aid of forceps and place it onto a designated sterile field.

Once the tumor is resected, tumor pathology is confirmed, and hemostasis is obtained, up to eight GLIADEL® Wafers (polifeprosan 20 with carmustine implant) may be placed to cover as much of the resection cavity as possible. Slight overlapping of the wafers is acceptable. Wafers broken in half may be used, but wafers broken in more than two pieces should be discarded in a biohazard container. Oxidized regenerated cellulose (Surgicel®) may be placed over the wafers to secure them against the cavity surface. After placement of the wafers, the resection cavity should be irrigated and the dura closed in a water tight fashion.

Unopened foil pouches may be kept at ambient room temperature for a maximum of six hours at a time.