Historically there have been only a limited number of chemotherapy drugs for the treatment of brain tumors. This is because of the potential side effects of drugs entering the brain and the difficulty of getting drugs to cross the blood-brain barrier, a “wall” that protects the brain by pumping toxins out of brain tissues and into the blood stream.
In recent years, however, researchers have expanded the use of chemotherapy as a next-line approach after surgery and radiation. Several drugs have now been shown to extend patients’ lives and improve the management of brain tumors.
The Brain Tumor Center at Memorial Sloan Kettering is actively helping to develop a number of these new drugs. In clinical trials for people with brain tumors, we are constantly testing new drugs and drug combinations to improve the options available. For many patients, a clinical trial offers the best approach to controlling a tumor.
Increasingly, research is showing that cancer cells with specific genetic mutations respond to particular drugs in certain ways. Our medical oncologists now use molecular information about individual patients’ tumors to determine which drugs are most likely to improve survival.
If you undergo a biopsy at the Brain Tumor Center, a pathologist will perform tests on cells from your tissue sample to look for mutations that may suggest which chemotherapy drug is most likely to be effective in controlling your tumor. Even if you do not begin chemotherapy right away, this tissue can be stored for a later time if the disease progresses.
Identifying certain molecular signatures in the tumor cells will also help your medical oncologist to determine whether you would be eligible to participate in certain clinical trials, which test new experimental approaches to treating tumors with specific molecular characteristics.
Temozolomide (Temodar®) is a standard drug for the treatment of glioblastoma that works by interfering with the cell division that makes a tumor grow. The drug has been shown to prolong survival and improve quality of life for patients newly diagnosed with glioblastoma. Because the basic building blocks of temozolomide are small molecules, the drug is able to cross the blood-brain barrier and reach tissues that other chemotherapy drugs cannot.
Memorial Sloan Kettering researchers are leading several ongoing clinical trials to study the best ways to use temozolomide for the treatment of glioblastoma and other high- and low-grade types of glioma.
Other drugs for the treatment of different types of brain tumors are carmustine (also called BCNU) and lomustine (CCNU). Both of these are also small molecules that can penetrate the blood-brain barrier.
Researchers at the Brain Tumor Center have also found that certain oligodendrogliomas are highly responsive to particular chemotherapy drugs, such as temozolomide, or a combination treatment known as PCV (procarbazine, CCNU, and vincristine).
Our researchers are using new types of drugs that block or interfere with cancer cell growth, particularly involving high-grade, malignant brain tumors that recur often or continue to grow despite treatment.
These drugs include:
- angiogenesis inhibitors such as bevacizumab (Avastin®), which prevent the growth of new blood vessels that supply tumors with nutrients and allow them to expand and spread
- growth factor inhibitors, which block tumor growth factors (such as epidermal growth factor) from reaching their receptors and interfere with cancer cell growth
- drugs that reduce the ability of cells with genetic mutations associated with malignancy to multiply and divide
Combining therapies holds promise not only for killing more cancer cells, but also for overcoming the resistance of some brain tumors to a single treatment.
We are investigating, for example, whether combining angiogenesis inhibitors and chemotherapy drugs such as irinotecan and temozolomide can enhance the effectiveness of treatment. Using angiogenesis inhibitors alongside new biologic agents such as signal transduction inhibitors also holds promise to enhance the effectiveness of radiation therapy. This combination approach has been shown to increase the sensitivity of brain tumors to radiation.
Some of our clinical trials are also testing the effectiveness of combining chemotherapy with radiation therapy.
Immunotherapy is an approach to drug development in which a patient’s own immune system is stimulated to selectively attack cancer cells. Basic scientists at the Brain Tumor Center are developing monoclonal antibodies that can attach to specific proteins on the surface of tumor cells. The immune system then recognizes these antibodies and eliminates the cancerous cells they are attached to.
Although this new approach to therapy is still under investigation, researchers anticipate that it will enable new approaches to treatment that are more targeted to cancer cells and cause fewer side effects.