Despite some progresses made in drug therapy, the glioblastoma remains to be one of the most fatal tumor diagnoses. So it doesn’t come as a surprise that a study introduced during the annual meeting of American Society of Clinical Oncology (ASCO 2010) last summer, caused quite a bit of a stir. In an open-label, randomized phase-III design a electrostimulation applied from externally through the calvaria was at least as good as chemotherapy in a branch of the control where the physicians allowed the choice of the individual best standard chemotherapy.
Continuous current through the calvaria
The electrostimulation system used during this study was the NovoTTF-system made by the Israeli manufacturer NovoCure. It is a portable, battery-operated device which generates alternating electric fields of low intensity. The electric fields are applied via electrodes on the scalp. The concept: the electric energy applied more or less continuously interferes with proliferation of the tumor cells thus slowing down the progress of the tumor.
237 patients with recurrent glioblastoma multiforme participated in this study introduced at the ASCO 2010. 120 of those patients were treated solely with electrostimulation, the others with the individually best suitable chemotherapy chosen by the treating physicians. In the intention-to-treat analysis, the total survival in the electrostimulation group was at 6.6 months, in the chemotherapy control group at 6 months – statistically no significant difference. In the per-protocol-population the difference of 7.8 versus 6.1 months was even more distinct and thus statistically significant. The one year survival rates were 23.6 respectively 20.8 percent. And also regarding the time until therapy failure there was a distinct almost not significant trend in favor of electrostimulation.
Better reaction and more favorable prognosis
As expected, the electrostimulation tolerance was significantly better that the chemotherapy tolerance. Except skin reaction, there was not a lot to report while in the control group, depending on the selected therapy scheme, hematological and other toxicities occurred. But as impressive the effect of the therapy in this study looked, the experts had a hard time sorting in this result. One of the reasons was that – despite the tendency of a better total survival, they were able to prove an objective reaction of the tumor in only 12 percent of the patients.
This was the main reason why the latest data of subgroup analyses now introduced at the congress of the Society for NeuroOncology in Montreal/Canada, was anticipated with quite a bit of excitement. What does it depend on whether a glioblastoma patient reacts to electrostimulation or not? Certain prognostic factors seem to play an important role: The advantage electrostimulation versus chemotherapy was more significant in patients with a good Karnofsky performance status, patients with an age below 60 and patients with the first until third recurrence. The median overall survival here was at 8.8 versus 6.6 months, the one year survival at 35 compared to 20 percent. In regard to the overall survival of patients not reacting to a Bevacizumab-therapy, the benefit was even more pronounced, the reason is not clear yet.
Will “electrotherapy plus Temozolomid“ be the new standard?
Well, quite a bit has happened in regard to the glioblastoma, also beyond electrotherapy; most of all establishing Temozolomid as a new standard. Since 2009, a complementary phase III study is made with glioblastoma patients comparing Temozolomid with a combination of Temozolomid and electrostimulation according to the Novo-TTF-procedure. If there will be an advantage of the combination we won’t have to wait much longer for a call to change the current guidelines.