Systemic Therapy Options in Glioblastoma

Transcript:Susan C. Pannullo, MD: After the surgery is performed on a patient with a newly-diagnosed glioblastoma, the important next steps include radiation therapy and chemotherapy. The radiation therapy is performed over the course of six weeks, five days a week. This has been based upon studies that have been done over the past several decades. It was found, in the early 1980s, that there was a significant survival benefit to be gained by adding radiation therapy to surgery for patients with newly-diagnosed glioblastoma. So, for the past several decades, radiation therapy has been employed for patients with this disease.

What has changed over the past several decades is that the radiation techniques have become much better, much more focused. This has allowed the patient to have a better response to radiation with fewer side effects and less damage to normal surrounding tissue.

The chemotherapy that’s utilized as standard of care for patients with newly-diagnosed glioblastoma is temozolomide. Temozolomide is an alkylating agent that crosses the blood-brain barrier. It is utilized in a specific way along with the radiation therapy. And then following a break after the 6 weeks of combined chemotherapy and radiation therapy, it is then used as a 5-day-on, 23-day-off regimen over the course of 6 months.

Steven A. Toms, MD: Once the surgery is complete and we have a histopathologic diagnosis of glioblastoma, we usually bring the patient back about two weeks later to get their stitches out, make sure the wound is healing. And if everything is going well, it’s time for them to sit down with the radiation oncologist and our medical oncologist to get started on therapy.

These days, the start of that therapy is known as the Stupp Protocol, whereby a patient gets about six weeks of radiotherapy—which includes Monday through Friday treatments that total about 60 gray of radiation along with daily temozolomide. The temozolomide dose that’s given is 75 mg/m2 to the patient—about half the dose that they get once the radiation is complete. They get that temozolomide, each day, along with the radiation treatment for about six weeks.

After the radiation and chemotherapy are done in their combined modality, we give the patient a little bit of a break of about three or four weeks before starting their monthly temozolomide, which typically includes 5 pills per month, and then 23 days off. So, every 4 weeks you get a cycle where Monday through Friday you take a daily dose of 150 mg/m2 temozolomide, and then 23 days off. We check a blood count to make sure we’re not having any problems with hematopoiesis—especially low platelets we often find with temozolomide. If the patient’s doing well, they go ahead and start their next cycle the next month.

Our practice has been to do at least 6 months of the monthly temozolomide after the radiotherapy. Very often, if the patient is doing well and shows no sign of progressive disease, we continue that up to 12 months. Where we run into problems, and with glioblastoma this is a common occurrence, is when we see tumor growing back—often in the four- to eight-month period. At that time, our team usually looks to other experimental protocols that are out there, as there’s nothing that is working consistently.

Now, bevacizumab has been introduced and has been available through the Food and Drug Administration for about seven or eight years now. And we do find, bevacizumab, or Avastin, is very good for our patients—especially if they have a lot of edema, a lot of swelling, and a lot of mass affecting the brain because it clamps down on the ability of the tumor to attract and build a new blood vessel system. That shuts down a lot of the swelling inside the brain. It tends to increase the patient’s survival a bit, although it’s mostly a tumor-static agent, as opposed to a tumor-cidle agent. It palliates the patient, gives them some extra time, but in and of itself it has not been as effective an agent as we’d hoped when the drug first came out.

And the other thing to remember when we use bevacizumab, is that we have to be sure that we’re not going to need to do any surgical procedures any time soon. Because once a patient is on bevacizumab, we need them to be off at least six to eight weeks before doing any surgery because there are bleeding and wound complications because of that antibody lingering for a long period of time and inhibiting the blood vessels that are necessary for wound healing.

Susan C. Pannullo, MD: Dexamethasone, which is a potent steroid medication, can be beneficial for patients who have glioblastoma because of its profound effects upon edema that can surround the tumor, and cause the patient to have severe neurologic symptoms.

Dexamethasone is an important tool in symptom control in patients who have glioblastoma. The edema that surrounds the patient’s brain tumor can often be the cause of worsening neurologic symptoms that the tumor itself would cause. Dexamethasone can be an important mechanism for improving symptoms that result. However, it’s imperative to consider the side-effect profile of dexamethasone—including immunosuppression. It’s equally important to consider the possibility that dexamethasone may play a role in tumor resistance to therapeutic agents.

For patients with newly-diagnosed glioblastoma, one of the important discussions, and one of the topics that is often raised in the course of both the multidisciplinary brain tumor conference, and also in the initial discussions with the patient who has a newly-diagnosed glioblastoma, and their family, is the opportunity to enroll in clinical trials. Because of the challenging nature of glioblastoma, and because of the paucity of therapies and minimal efficacy of some of them, it’s very important to consider clinical trials in this patient population.

Transcript Edited for Clarity