The Role of Chemoradiotherapy in Glioblastoma

Transcript:Suriya Jeyapalan, MD, MPH: The dosing of Temodar (temozolomide) in newly diagnosed GBM patients basically takes 2 forms. There’s up-front therapy, when we dose Temodar with radiation. And for everybody in the audience who’s hearing this, we have to understand that when the Canadians and the Europeans designed this trial, no chemotherapy had ever been shown to impact the treatment of GBMs. And Roger Stupp in Switzerland, in a get-together with the Canadians, decided that since surgery and radiation were really the only 2 things that worked, we know some chemotherapy agents (ie, alkylating agents) will enhance the effect of radiation. He wanted to use this as a radiation sensitizer. And one of the things to remember with the original trials: it was not done in America.

I think a lot of people are confused how to use Temodar with radiation. You really need to give the Temodar an hour before radiation. The half-life of Temodar is about 3 to 5 hours; it doesn’t last in your system. Really, it’s out of your system within 24 hours. I’ve noticed when I’ve gotten referrals from community oncologists, sometimes even other major tertiary care centers, that they’re telling patients to take the Temodar at nighttime when they get radiation. Well, then it’ll be out of their system by the time they get the radiation the next day. So, you have to realize it’s a radiation sensitizer. You want to take it an hour before the radiation so it’s in the bloodstream, in the body, it’s attacking the tumor, and then the radiation is affecting it as well.

You have to take it on an empty stomach because if you have food in your stomach, it decreases the absorption of Temodar. So, what I tell people is take your antinausea pill an hour before the Temodar, don’t eat for an hour, take your Temodar and don’t eat for another hour, and then have your radiation. And then, you do that for 6 weeks. The other thing to remember, and I joke around with my radiation oncology colleagues all the time with this, is although you only receive radiation Monday through Friday—because my radiation oncology buddies feel that tumors don’t grow on the weekend—I don’t feel that way. As your oncologist, take your chemotherapy on Saturday and Sunday, too. So, you take the Temodar 7 days a week. On Saturday and Sunday, you can take it whenever you want, if you want to take it at bedtime. But Monday through Friday with the radiation, I want the patients to take it an hour before their radiation.

Now, after the patient finishes that 6-week course, they get a month off. And then, they start the adjuvant treatment of Temodar. Now, in the original trial, they did it for 6 months. And that was because, essentially, they weren’t really sure how long to treat people. There were some cost concerns, too, because you’re dealing with more of a national healthcare system. So, they basically budgeted for about 6 months after the 6 weeks of radiation, and they showed the survival advantage with that. In America, I’ve seen people use it for a year. Before 2015, all we had was Temodar. I’ve had some patients go on it for years, and I think that’s something that people can talk about. But the dosing schedule in the adjuvant setting is 5 days out of every 28 days. Usually, I meet the patient once a month. I check their blood counts, check how they’re doing, check their labs, and then we dose them based on their height and their weight. The first month we dose them 150 mg/m2 and see how they tolerate it. And the next month, if the blood counts show they tolerate it, then we’ll increase the dose to 200 mg/m2. Whether or not you want to go past the 6 months or not—I know most people in the United States try to do it for a year, sometimes people go a little further—that’s really up to the oncologist. And it’s really based on anecdotal evidence. But the trial itself was for 6 months.

Maciej Mrugala, MD, PhD, MPH: MGMT methylation status is an important prognostic and predictive factor in glioblastoma, and we now recommend that every patient who has newly diagnosed glioblastoma get tested for this mutation. We know that the addition of temozolomide to patients who do have the methylation status significantly prolongs survival. So, for that reason, testing is crucial because that allows us to prescribe appropriate therapy to the patient. In patients who do not have methylation, the benefit is rather minimal, and depending on the situation, it may not be a bad idea to completely bypass progression of temozolomide to patients who do not have the methylation—as the toxicity of the treatment might actually outweigh the benefit to the patient. At this day and age, I think that in every single case of glioblastoma, MGMT methylation status should be assessed because it’s really important and crucial in clinical decision making.

Daniela Bota, MD: The standard-of-care treatment for newly diagnosed patients with glioblastoma is what we call the Stupp regimen, and this is the regimen that, under the guidance of Dr. Roger Stupp, was established and approved in 2005. It consists of 6 weeks of radiation with daily temozolomide. The total dose of radiation is 60 grades. They are giving 2 grades a day, Monday to Friday, so that’s how we come to the number of 60. The chemotherapy with temozolomide is given every day, including Saturdays and Sundays.

We allow the patients, at the end of 6 weeks, a total 4-week break to recover from the side effects of the radiation and the daily temozolomide. And then, the patients embark on another 6 to 12 months of therapy with temozolomide. For this second stage of treatment, the patients receive the temozolomide at a higher dose 5 days every 28 days. The treatment is very well tolerated, both the one that we do with radiation and the one that we do after the radiation. We see mild side effects, some of them being local skin reaction because of the radiation, fatigue, nausea, and decrease on the blood count, such as platelets and white blood cells. When we move on to the Temodar as a single agent, we tend to see fatigue, we tend to see changes on the blood count, we tend to see nausea—and we’ll talk about that a little bit later. Also, we have seen constipation. So, those are the general side effects. They are in less than 8% of the patients, for each individual side effect. In general, this treatment is very well tolerated.

It is important for us, as physicians, sometimes to prevent those side effects. So, in our practice, we usually give a nausea medication to be taken every day before the chemotherapy is administered. In this way, we reduce the incidence of nausea in our patients. For the constipation, it’s important to have a dietary consultant onboard and instruct the patients how can they prevent it—with an increased consummation of fibers and fruits and appropriate intake of water. For the low blood counts, our practice is to follow the blood count every week during the radiation. During the temozolomide cycles, which take place after the radiation, we usually get lab work at day 21 and day 28 every cycle and really start the chemotherapy only if the blood counts have recovered. If they have not recovered completely, we have the choice of waiting and restarting the chemotherapy after they have recovered. And if the chemotherapy side effects are, on rare occasion, quite profound and it takes a long time for the patients to recover or the counts go very low, we also reduce the dose of chemotherapy for the next cycles.

Transcript Edited for Clarity