A brain tumor is an abnormal growth of cells in the brain and there are many different types of them. In general, they are described as benign or malignant, and as primary or metastatic.

Benign Versus Malignant Brain Tumors

A benign tumor contains noncancerous cells, may not be life-threatening, and may be treated primarily with surgery. A malignant tumor contains cancerous cells, often grows rapidly, and is life-threatening.

Primary Versus Metastatic Brain Tumors

A brain tumor can start in the brain or in other parts of the body. If the tumor starts in the brain, it is called a primary brain tumor. Primary tumors can be benign or malignant. If cancer cells that originate in other parts of the body (such as the breast, lung, or colon) travel to the brain, they are called metastatic brain tumors. All metastatic brain tumors are malignant.

GLIADEL Wafer is not indicated in patients with metastatic brain tumors.

Types of Gliomas

Glioma is a general term used to describe a tumor that grows out of the brain’s supportive cells called glial cells. Gliomas are the most common type of primary malignant brain tumor.

Astrocytomas are the most common type of glioma found in adults. These tumors originate from astrocytes – the star-shaped cells that create the supportive tissue of the brain.

Low-Grade astrocytomas tend to invade surrounding tissue and grow at a relatively slow pace.

Anaplastic astrocytomas are rare tumors that tend to have tentacle- like projections that grow into surrounding tissue, making them difficult to completely remove during surgery.

Glioblastoma multiforme (GBM) are fast-growing, aggressive malignant (Grade IV) tumors that are infiltrative and invade into nearby regions of the brain. There are two types of glioblastoma—primary, or de novo, and secondary. Primary glioblastomas begin as a grade IV tumor with no evidence of a lower grade precursor. Secondary tumors are those which originate as a lower-grade tumor and evolve into a grade IV tumor.

GLIADEL Wafer is not indicated FOR USE IN LOW-GRADE ASTROCYTOMAS.

Oligodendrogliomas: These tumors originate from the cell types which comprise the supportive or glial tissue of the brain. These cell types are known as oligodendrocytes. Oligodendrocytes have a “short arm” fried egg appearance when viewed under the microscope, while astrocytomas have a “long arm” star-like appearance to them.

Anaplastic oligodendrogliomas are aggressive tumors that arise in oligodendrocytes that grow quickly. Anaplastic oligodendrogliomas are considered high-grade (Grade III).

Anaplastic oligoastrocytoma is a brain tumor which forms into a mass by the rapid increase of two types of brain cells (oligodendrocytes and astrocytes). Anaplastic oligoastrocytomas can occasionally contain grade IV astrocytoma cells.

INDICATIONS

GLIADEL Wafer (carmustine implant) is indicated for the treatment of patients with newly-diagnosed high-grade glioma as an adjunct to surgery and radiation.

GLIADEL Wafer is also indicated in patients with recurrent glioblastoma 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 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.

ADVERSE REACTIONS

The most common adverse reactions in newly-diagnosed high-grade glioma patients are cerebral edema, asthenia, nausea, vomiting, constipation, wound healing abnormalities and depression.

The most common adverse reactions in recurrent high-grade glioma patients are urinary tract infection, wound healing abnormalities and fever.

The Important Safety Information does not include all the information needed to use GLIADEL safely and effectively. For additional safety information, please consult the full Prescribing Information for GLIADEL.

To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc. at 1-800-461-7449 or FDA at www.fda.gov/medwatch or call 1-800-FDA-1088.