Treatment > Temozolomide Clinical Trials

Meeting Abstract

Safety profile and activity of high-dose temozolomide given daily x 3 every 2 weeks in patients with primary brain tumors

Eric Raymond, Karina Vera, Latifa Djafari, Laure Felizot, Sandrine Faivre, Kamel Djazouli

Institute Gustave Roussy, Villejuif, France; Schering-Plough, Levallois-Perret, France

Temozolomide (Temodal-TMZ) has shown activity and limited toxicity in patients (pts) with primary brain tumors (PBT) at doses of 150-200 mg/m2/d1-5 q4weeks. 
We explored safety and activity of a new alternative high-dose intensity regimen of TMZ. 
TMZ was given orally at escalated dosages on days 1-3 and 14-16 every 28 days (one cycle). 
Four groups of at least 7 evaluable patients with PBT received TMZ at doses ranging 200-350 mg/m2/day(d) (8mg oral ondansetron 30-60min prior to TMZ). 
Blood count with differential (NCI-CTC) was assessed weekly for toxicity and brain MRI was performed at baseline then every 3 cycles (McDonalds criteria) for activity. 
Thirty-eight patients (male/female: 28/10; mean age: 49, range 17-73, PS 0-1: 27) including 10 glioblastomas, 9 astrocytomas, 11 oligodendrogliomas, 5 oligoastrocytomas, 1 ganglioglioma, 1 pineoblastoma, and 1 malignant meningioma were entered. 
Twenty-four pts had prior surgery including 8 complete resections, 16 partial resections, and 14 stereotaxic biopsies. Thirty-four and 16 pts had prior radiotherapy and chemotherapy, respectively. 
Median prior chemotherapy number including nitrosoureas was 1 (1-3). 
Seven (24 cycles), 8 (36 cycles), 12 (44 cycles), and 11 pts (86 cycles) received 200, 250, 300, and 350 mg/m2/d TMZ, respectively. 
Gr2-3 thrombocytopenia was observed in 1/7, 0/7, 3/11 and 6/10 evaluable pts treated with 200, 250, 300, and 350 mg/m2/d TMZ, respectively. 
Gr2-3 neutropenia was observed in 2/7, 1/7, 0/11, 3/10 pts treated with 200, 250, 300, and 350 mg/m2/d TMZ, respectively. 
Gr4 neutropenia (1 febrile) was observed in 2 pts at the dose of 350 mg/m2/d TMZ. 
Tumor control (partial response-PR+tumor stabilization-SD) was observed in 2/6 (2SD), 4/6 (1PR+3SD), 4/11 (1CR+2PR+1SD), and 10/10 (5PR+5SD) evaluable pts treated with 200, 250, 300, and 350 mg/m2/d TMZ, respectively. 
In summary, high-dose intensity 300 mg/m2/dx3 q2w TMZ is safe with evidence of activity in chemonaive and nitrosourea-pretreated pts with PBT.

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