Radiation and concurrent temozolomide followed by rotational multi-agent chemotherapy for glioblastoma (GBM) patients

Abstract

2068 Background: GBM is the most lethal type of brain tumor with a 1 yr median survival. We hypothesized that GBM patients who receive adjuvant rotational multi-agent chemotherapy (temozolomide, CCNU, and CPT-11) have improved overall survival when compared to patients receiving single agent adjuvant regimens (carmustine, temozolomide). Methods: We conducted an IRB-approved retrospective data analysis of 80 primary GBM patients who received radiation therapy and concurrent temozolomide followed by 12 mos of adjuvant rotational multi-agent chemotherapy. All patients with the intent to treat were included in the analysis. The survival experience of the Duke cohort was examined within specific patient subgroups defined by the original Radiation Therapy Oncology Group (RTOG) recursive partition analysis (RPA). These data were compared to the recently published Stupp RPA analysis (JCO 2006) and the RTOG trial (radiation alone). Results: 73% were male. Mean age was 52 yrs (range 21–76 yrs); 39 % were < 50 yrs.. 82% were white. WHO performance status was: 0, 14%; 1, 62%; 2, 20%; and 3, 4%. Overall survival was 59% (95% CI: 49%, 71%) at 1 yr and 31% (23%, 43%) at 2 yrs. Median survival was 65.1 wks (49.7, 78.9) with median follow-up of 122.1 wks.. No difference in the 2-yr overall survival rate in RPA classes III-IV was detected between the Duke and Stupp regimens (p>0.4733), but 66% (33, 77) of the Duke rotational therapy GBM patients are living longer than the RTOG patients (p > 0.0086). Univariate Cox Hazard ratio of 1.27 (0.522, 3.08) did not correlate MGMT status with survival (p > 0.60). Conclusions: (1) Concurrent Temozolomide and radiation followed by rotational chemotherapy is an effective therapy compared to recent published gold standard adjuvant regimens. (2) Concurrent Temozolomide and radiation followed by rotational chemotherapy resulted in a statistically significant survival benefit compared to RTOG trial. (3) Lack of correlation between MGMT and overall survival suggests that agents whose damage is not repaired by MGMT may be an important therapeutic approach. (4) Future prospective randomized trials with concurrent Temozolomide and radiation must compare post radiation multi-modality regimens. No significant financial relationships to disclose.