Treatment > Procarbazine · Temozolomide Clinical Trials

Meeting Abstract

Randomized Trial of Temodal (TEM) Vs. Procarbazine (PCB) in Glioblastoma Multiforme (GBM) at First Relapse

R Albright, M Brada, J Brunner, MH Dugan, K Fink, R Fredericks, VA Levin, J Olson, M Prados, A Spence, N Yue, A Yung, S Zaknoen

Despite combined modality approaches with surgery, radiation therapy, and chemotherapy, survival of patients with GBM, the most common primary brain tumor, remains poor. 
Temodal (temozolomide), an imidazotetrazine, is an oral methylating agent with activity in malignant gliomas. 
TEM crosses the blood brain barrier, and is well tolerated with minimal myelosuppression. 
Previous phase I studies had demonstrated its efficacy in a wide variety of tumors including malignant gliomas. 
A recent phase II study has demonstrated activity in recurrent anaplastic astrocytoma (ASCO Proceedings 16:384a, 1997). This randomized phase II trial is designed to compare efficacy and safety of TEM to PCB as a standard agent in adult GBM at first relapse. 
Patients must have histologically proven GBM, a KPS of 70 or better, and unequivocal tumor recurrence or progression by Gd-enhanced MRI. 
Patients were given 150-200 mg/m2/d x 5d, every 28d, versus PCB 125-150 mg/m2/d x 28d, every 56d. 
Primary end point was progression free survival (PFS) at 6 months with secondary end points including objective response, overall survival and improvement in health related quality of life (HQL). 
MRI was performed every 2 months to access tumor status, HQL was assessed monthly using EORTC QLQC30 and a brain tumor module. 
Histology and MRI scans were reviewed centrally. 
Between 3/95 and 10/97, 225 patients (112 TEM, 113 PCB) were enrolled into the study. 
Patient characteristics were similar between the two groups: median age 52/51 yrs.; KPS >70 78/74%; prior nitrosourea-based chemotherapy 65/68% for TEM and PCB respectively. 
PFS at 6 months was 21% for TEM and 8% for PCB with a p-value of 0.008. 
Median PFS for TEM of 2.89 months was significantly longer than that for PCB of 1.88 months, with a p-value of 0.0063. Six month overall survival rate for TEM was 60% versus 44% for PCB, with a p-value of 0.019. 
More TEM patients showed improved or stable HQL than PCB patients at months 3 and 6. 
Major hematologic toxicity was thrombocytopenia, while nausea, vomiting and constipation were common non-hemotalogic toxicity. 
These results show that TEM is well tolerated and has significantly better PFS than PCB in patients with recurrent GBM. TEM patients also had a longer survival and better overall QOL.

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