OBJECT: The objective of this study was to report the authors' experience with 
the long-term administration of temozolomide (TMZ; > 6 cycles, up to 101) in 
patients with newly diagnosed glioblastoma and to analyze its feasibility and 
safety as well as its impact on survival. The authors also compared data 
obtained from the group of patients undergoing long-term TMZ treatment with data 
from patients treated with a standard TMZ protocol.
METHODS: A retrospective analysis was conducted of 37 patients who underwent 
operations for glioblastoma between 2004 and 2012. Volumetric analysis of 
postoperative Gd-enhanced MR images, obtained within 48 hours, confirmed tumor 
gross-total resection (GTR) in all but 2 patients. All patients received the 
first cycle of TMZ at a dosage of 150 mg/m(2) starting on the second or third 
postsurgical day. Afterward, patients received concomitant radiochemotherapy 
according to the Stupp protocol. With regard to adjuvant TMZ therapy, the 19 
patients in Group A, aged 30-72 years (mean 56.1 years), received 150 mg/m(2) 
for 5 days every 28 days for more than 6 cycles (range 7-101 cycles). The 18 
patients in Group B, aged 46-82 years (mean 64.8 years), received the same dose, 
but for no more than 6 cycles. O(6)-methylguanine-DNA methyltransferase (MGMT) 
promoter methylation status was analyzed for both groups and correlated with 
overall survival (OS) and progression-free survival (PFS). The impact of age, 
sex, Karnofsky Performance Scale score, and Ki 67 staining were also considered.
RESULTS: All patients but 1 in Group A survived at least 18 months (range 18-101 
months), and patients in Group B survived no more than 17 months (range 2-17 
months). The long-term survivors (Group A), defined as patients who survived at 
least 12 months after diagnosis, were 51.3% of the total (19/37). Kaplan-Meier 
curve analysis showed that patients treated with more than 6 TMZ cycles had OS 
and PFS that was significantly longer than patients receiving standard treatment 
(median OS 28 months vs 8 months, respectively; p = 0.0001; median PFS 20 months 
vs 4 months, respectively; p = 0.0002). By univariate and multivariate Cox 
proportional hazard regression analysis, MGMT methylation status and number of 
TMZ cycles appeared to be survival prognostic factors in patients with 
glioblastoma. After controlling for MGMT status, highly significant differences 
related to OS and PFS between patients with standard and long-term TMZ treatment 
were still detected. Furthermore, in Group A and B, the statistical correlation 
of MGMT status to the number of TMZ cycles showed a significant difference only 
in Group A patients, suggesting that MGMT promoter methylation was predictive of 
response for long-term TMZ treatment. Prolonged therapy did not confer 
hematological toxicity or opportunistic infections in either patient group.
CONCLUSIONS: This study describes the longest experience so far reported with 
TMZ in patients with newly diagnosed glioblastomas, with as many as 101 cycles, 
who were treated using GTR. Statistically significant data confirm that median 
survival correlates with MGMT promoter methylation status as well as with the 
number of TMZ cycles administered. Long-term TMZ therapy appears feasible and 
safe.