Insights From: Susan C. Pannullo, MD, Weill Cornell Brain and Spine Center; Steven A. Toms, MD, Geisinger Health System
Steven A. Toms, MD: Almost always in patients with glioblastoma, the glioblastoma eventually recurs. Many times this is within the first 6 to 12 months of the patient finishing their radiation and temozolomide.
When a patient comes back with a recurrent glioblastoma, the question that comes to the multidisciplinary team of the radiation oncologist, the neuro or medical oncologist, and the surgeon first is: is further surgery warranted. When we look at this, we usually look at it together as a team, and we ask the same questions we have with a newly-diagnosed patient. How much disease is there? How much mass effect and swelling do we have? Certainly, if there’s a large tumor bulk with mass effect and swelling and the patient has a good Karnofsky performance level, and is doing well, a second surgery is often warranted. If there’s only a small amount of disease without mass effect, and there’s no question about the diagnosis, then we usually bypass surgery at that time.
Other reasons to contemplate repeat surgery: are there clinical trials that need tissue such as a vaccine trial they might be eligible for? That pushes us a little bit more toward surgery.
In those cases in which the tumor burden is very small, and there’s minimal or no mass effect, and there are no seizures that are difficult to control, we usually move on to a second-line chemotherapy, and sometimes consider additional radiotherapy.
Susan C. Pannullo, MD: Bevacizumab is a recombinant monoclonal humanized antibody that is often used in patients with glioblastoma. The drug was given accelerated FDA approval in 2009, and is often employed in patients with recurrent disease. In addition, it has been studied in the upfront setting in these patients.
In many trials, bevacizumab has been given as 10 mg/kg dosing every two weeks, and this schema is often utilized in the clinic as well.
Bevacizumab has been utilized in both the recurrent and upfront setting with varying results. The initial studies, in 2009, for patients with recurrent glioblastoma, suggested that there was progression-free survival benefit, which may translate to improvement in quality of life.
Data presented at the recent Society for Neuro-Oncology meeting demonstrate a failure of bevacizumab to improve survival in combination with CCNU, or lomustine—an alkylated agent—compared with that alkylating agent CCNU alone, despite an improvement in progression-free survival.
Steven A. Toms, MD: Once radiotherapy and bevacizumab had been trialed, and proved to not be effective, we have a few other options left. The FDA-approved options include the nitrosoureas, such as BCNU or CCNU. Back when I was at Cleveland Clinic, we had some success with Tarceva (erlotinib) as another agent.
But, what we try to look for, when a patient has recurrent disease, is to try to get them into a clinical trial either within our own group, or with some of our collaborating institutions nearby in Philadelphia or New York if it’s a trial we don’t have available. Unfortunately, there are not terribly many things that seem to work well with recurrent glioblastoma. Again, if the patient hasn’t been using Optune, I’d reopen that discussion with the patient because we do know that Optune does have efficacy in recurrent glioblastoma.
But there’s still some resistance among some oncologists and some patients to using this device. On the oncologist’s side, it’s usually the oncologist doesn’t yet believe that this mechanism is a mechanism that works. There’s still a bit of resistance out there—as I had many years ago. And then the other resistance you sometimes get is from patients and families.
If the patient resists, it’s not worth using the Optune device. The other thing that our team finds very important is that the patient has a good family network. Because if the patient has a good support group, it’s much easier for them to be compliant. If they are complying with the device, they tend to have a better result. Once a patient becomes non-compliant to wearing the device, only 50% to 60% of the time, it probably has very little efficacy.