e12521 Background: Temozolomide (TMZ), an oral imidazotetrazine second-generation alkylating agent that enters the cerebrospinal fluid, has demonstrated antitumor activity in high-grade glioma when given as adjuvant therapy concomitant with RT, and then alone (Stupp R., NEJM,2005). Methods: The aim was to evaluate disease free (DFS) overall survival (OS) and safety TMZ in combination with RT in high-grade cerebral glioma, after surgery. RT to limited fields was administered once a day at 2 Gy/fraction, 5 days a week for 6 weeks, for a total of 60 Gy, with concomitant TMZ 75 mg/sqm daily, followed by 6 cycles of TMZ 150-200 mg/sqm daily on days 1->5 q 28 days. Results: From 11/2004 to 9/2007, we accrued 23 consecutive pts, median age 63 years (range 34-72), 18 M, 5 F; ECOG PS was 0 in 21 pts and 3 in remaining 2. 10 pts. (43,5%) had R0 resection; 7.(30,4%) underwent not-radical resection, and 6 (26,1%) were considered inoperable. Pathology was as follows: glioblastoma 14 (60,9%), anaplastic astrocytoma 4 (17,4%), astrocytoma GII 4 (17,4%), anaplastic oligodendroglyoma 1 (4,3%). 19 pts (82,6%) completed concomitant RT/CT treatment and 8 (34,7%) also completed the subsequent 6 cycles of TMZ as planned. 2 pts. (8,7%), R2 resected and inoperable respectively, suspended TMZ/RT program due to early progression and the other 2 (8,7%) PS 3 pts., received no treatment. 10/19 (52,6%) pts., who completed the first part of the planned treatment, delayed TMZ cause of PD after a median of 3 cycles (range 1-5); 1/19 (5,3%) did not receive TMZ due to PD after TMZ/RT. No G3/4 toxicity occurred DFS was 5,5 + months (range 1-47+). Second line CT with PCV was given to 5/23 pts (21,7%), TMZ dose dense in 2/23 (8,7%) and 1/23 (4,3%) underwent third line CT with fotemustine.1/23 (4,3%)was treated with rescue surgeryand 2/23 (8,7%) with stereotassic radiotherapy. Median OS was 10,1+ months (range 1,1-72+). Conclusions: Even if debulking surgery occurred in only 74% pts, this schedule is safe, feasible and active in malignant glioma. During following years, due to improvement of OS, more pts underwent further lines of CT or stereotassic radiotherapy or novel surgery, unthinkable since few years ago.