Glioblastoma and Increased Survival with Longer Chemotherapy Duration

Abstract

Background: The five year survival for patients with glioblastoma (GBM) is low at approximately 4.7%. Radiotherapy plus concomitant and adjuvant temozolomide (TMZ) remain the standard of care. The optimal duration of therapy with TMZ is unknown, though treatment periods of six months, 12 months and longer have been utilized. Whether or not there is a benefit with longer treatment duration is controversial. This study sought to evaluate overall survival benefit of two years treatment. Methods: This was a retrospective chart review of all patients diagnosed with GBM who were treated at a regional cancer referral center. These patients were treated with TMZ for up to two years between January 1, 2002 and December 31, 2011. Survival was calculated as the time from initial surgical diagnosis until death. The Kaplan-Meier method with log-rank test was used to estimate the progression-free survival (PFS) as well as the overall survival (OS) distribution of patients after treatment. The results were compared to historical controls and data from previous clinical trials of pts treated up to one year. Results: Data from 56 patients were evaluated, the majority of whom had gross total resection and had external pathology review confirming the diagnosis of GBM. The OS probability was 54% (SE = 0.068) at one year, 28.3% (SE = 0.064) at two years, 17.8% (SE = 0.059) at three years and 4% (SE=0.041) at five years. The median PFS time in this study group was eight months (95% CI = 4.0 - 9.0 mo). The probability of no progression at two years was 8.6% (SE = 0.05). Seven patients (12.5%) were treated with TMZ for two years. The median time-to-progression among these patients was 28 months (95% CI = 5.0-28.0). These patients showed an increased survival probability at three years compared to patients who did not receive the two year treatment of TMZ (log-rank test χ2 (1, N=56) = 19.2, p < 0.0001). Conclusions: This study suggests that there may be an advantage for a longer duration of TMZ therapy among patients with GBM. In this study, treatment with TMZ for two years was associated with increased survival. While we consider the sample size to be too small for generalization, a prospective, multicenter study with a larger sample size might better evaluate the question of duration of TMZ therapy, particularly if both clinical and basic science data are paired.