Temozolomide in glioblastoma: results of administration at first relapse and in newly diagnosed cases. Is still proposable an alternative schedule to concomitant protocol?

Abstract

To evaluate if timing of chemotherapy with Temozolomide (TMZ) was able to modify the outcome of glioblastoma (GBM), we analyzed two comparable series of supratentorial GBM patients, treated with surgery and radiotherapy, in which the administration of TMZ has been performed in the first group at first relapse and in the second group in newly diagnosed cases. The end-points were the median survival, the time tumor progression (TTP) and also the Karnofsky (KPS) scale and the Mini Mental State Examination (MMSE) scale at follow-up. From December 1999 to December 2001 30 patients with recurrent GBM received TMZ until progression. From January 2002 to January 2004 38 newly diagnosed patients received a first cycle of TMZ immediately after surgery, and additional cycles after completing radiotherapy until recurrence. In order to obtain a greater drug exposure we adopted a once-daily 10 days schedule of TMZ every 28 days as follows: 150 mg/m(2)/day (day 1-5) and 75 mg/m(2)/day (day 6-10). The first group had a median overall survival of 14 months and a median TTP of 6. The second group had a median survival of 16 months and a median TTP of 10. The difference of TTP was statistically significant (P < 0.001), while the overall survival was not. The values of KPS and MMSE at 12 months demonstrated a better quality of life in the second group (P < 0.01). Our regimen permitted to cover the therapeutic "window" between surgery and the beginning of radiotherapy in newly diagnosed cases and is well tolerated by the patients with limited side effects. We will propose as alternative option when the concomitant radio-chemotherapic protocol is not feasible.

The efficacy of temozolomide for recurrent glioblastoma multiforme

“…Data for OS‐6 were available for analysis from a total of 672 patients enrolled in 11 trials. The OS‐6 rate ranged from 46.0% to 93.3%, with the lowest noted in a trial using the standard schedule , and the highest noted in a trial using the high dose metronomic schedule . The overall OS‐6 rate was 65.0% (95% CI: 57.4–71.9%) determined by random‐effects model (heterogeneity analysis: Q = 32.461, I 2 = 69.193, P < 0.001).…”

Randomized Study of Postoperative Radiotherapy and Simultaneous Temozolomide without Adjuvant Chemotherapy for Glioblastoma

“…In addition, many factors will probably change during the course of the disease. Therefore, the optimal treatment schedule including neoadjuvant [2,6], metronomic [15] or dose-intensified TMZ [31] application can only be determined in large, randomized trials such as those which have been performed for anaplastic oligodendrogliomas [5,28]. As a consequence, a 4-arm trial in anaplastic astrocytoma which will allow to separate the effects of adjuvant and concurrent TMZ has been started (EORTC 26503, CATNON-trial), and a 2-arm trial in glioblastoma (RTOG trial 0525) that examines the effect of dose-intensified adjuvant TMZ has been performed.…”

Recent therapeutic advances and insights of recurrent glioblastoma multiforme

“…Several clinical trials tried to evaluate the efficacy of TMZ in recurrent GBM with both standard 5-day schedule (24)(25)(26)(27)(28)(29)(30) and dose-dense schedule and showed varied results (31)(32)(33)(34)(35)(36)(37)(38). With respect to tumor response, clinical benefit rate (complete response, partial response and stable disease) ranged from 36.7% to 90.5%.…”