Administering the chemotherapy drug temozolomide to patients with a common and aggressive form of primary brain tumor--glioblastoma--in combination with radiotherapy (RT) increases their life expectancy for up to five years, compared to RT alone, according to research published online in the Lancet Oncology.
For more than 30 years, post-operative RT was the standard treatment for glioblastoma, but offered only modest survival benefits to patients, according the authors. The average life-expectancy of patients with glioblastoma was nine months.
In 2004, after many disappointing attempts with drug therapy, the international phase III EORTC-NCIC trial showed some promising results in this difficult setting where use of combined treatment with RT and temozolomide (TMZ) reduced the risk of dying from glioblastoma by 37 percent (HR for death 0.63) compared with radiotherapy alone. At 2 years, 27 percent of patients receiving temozolomide in combination with RT (TMZ/RT) were alive, compared with just 10 percent of patients being treated with RT alone. However, whether this survival benefit would persist over time was unknown, which is why the researchers said they undertook the study.
Roger Stupp, MD, from the Multidisciplinary Oncology Center at the University of Lausanne Hospitals in Lausanne, Switzerland, and colleagues studied the long-term five-year outcomes of patients involved in the original EORTC-NCIC trial. The authors also examined whether clinical factors and the molecular profile of the tumors would identify patients with particularly good survival or response to chemotherapy.
The researchers found that at three years, 16 percent of patients receiving TMZ/RT were alive compared with only 4 percent of patients having RT alone. At four years, overall survival data after combined treatment were 12.1 percent compared with 3 percent for RT alone and at five years, 9.8 versus 1.9 percent, respectively.
Importantly, the authors noted that the improvement in survival was seen across all clinical prognostic subgroups, even in patients considered to have a poor diagnosis-such as more elderly patients or patients whose tumor could not be removed.
They found that the overall survival data were best in patients being treated with TMZ/RT whose tumours carried an inactivated MGMT gene (0-6-methylguanine-DNA methyltransferase). Almost half of the patients were alive after two years and they also showed a persistent survival advantage at three, four and five years. The authors suggest that testing tumours for the methylation status of the MGMT gene would allow the selection of patients most likely to benefit from this treatment.
Despite the improvement--with a substantial proportion of patients surviving for several years after treatment with TMZ/RT--most still died, according to Stupp and colleagues.
The authors also noted no difference in the pattern of recurrence between patients treated with RT alone or TMZ/RT, and caution that upfront combined therapy may be effective in reducing tumor bulk and aggressiveness, but it does not truly modify the natural behavior of the disease and thus is unlikely to lead to a cure.