ACTR-06. DOSE DENSE TEMOZOLOMIDE (TMZ) AS INITIAL TREATMENT FOR HIGH-RISK OLIGODENDROGLIAL TUMORS: LONG-TERM RESULTS OF A PHASE II AINO (ITALIAN ASSOCIATION FOR NEURO-ONCOLOGY) STUDY

Abstract

BACKGROUND: High-risk low grade gliomas (LGGs) are characterized by either incomplete resection or progression following observation with MRI. Temozolomide (TMZ) alone after surgery represents an option to delay radiotherapy and risk of cognitive impairment. Thus far, the efficacy of dose dense TMZ in LGGs is not well known. METHODS: Between 2006 and 2010 a single arm phase II study on 60 patients with high risk WHO grade II oligodendroglioma or oligoastrocytoma, age ≥ 18 years, KPS ≥70, measurable tumor on FLAIR MRI and absent or mild enhancement was performed. Primary endpoint was response rate according to RANO criteria and secondary endpoints were seizure control, progression-free survival (PFS), and overall survival (OS). RESULTS: Median number of TMZ cycles was 11 (2-18) with median follow-up of 64 months (7-112). Response consisted in PR 23/60 (38%), MR 12/60 (20%), SD 21/60 (35%), and PD 4/60 (7%). A significant seizure reduction was observed in 34/39 patients (87%) with maximal reduction either observed earlier than MRI or associated with a stable radiological disease. Median PFS was 40 months with 32% of patients progression-free at 60 months. MGMT methylation was associated with higher response (p=0.002) and longer PFS (p=0.019). 1p-19q codeletion and IDH 1/2 mutations tended to be associated with both response and PFS. Thirty-one (51.7%) patients decreased dose dense TMZ, 8 (13.3%) switched to standard schedule, and 6 (10%) discontinued the drug. Median survival from start of TMZ and subsequent salvage treatments was 92 months. IDH 1/2 mutations were significantly associated with longer survival. CONCLUSIONS: Response and outcome of high risk oligodendroglial tumors following dose dense TMZ are similar to that observed in studies employing the standard regimen. MGMT methylation is a predictive factor for both response and PFS. This is the first trial investigating seizure control as a secondary endpoint.