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

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.